curcumin and Obesity

Metabolic diseases have become a serious threat to human health worldwide. It is crucial to look for effective drugs from natural products to treat metabolic diseases. Curcumin, a natural polyphenolic compound, is mainly obtained from the rhizomes of the genus

Topics: Curcumin; Diabetes Mellitus, Type 2; Humans; Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Obesity

Obesity, as an unfavorable consequence of our modern lifestyle, can promote the emergence of other disorders, like diabetes and cardiovascular disease, that negatively impact quality of life. Therefore, prevention and treatment of obesity and its related comorbidities are critical. Lifestyle modification is the first and most important step but, in practical terms, presents a major challenge to many patients. So, the development of new strategies and therapies is critical for these patients. Although herbal bioactive compounds have recently gained attention for their ability to prevent and treat conditions related to obesity, no ideal pharmacological treatment has been found to treat obesity. Curcumin, one of the compounds extracted from turmeric, is a well-studied active herbal extract; however, its poor bioavailability and solubility in water, instability against temperature, light and pH fluctuations and rapid excretion limit its therapeutic application. Curcumin modification can, however, provide novel analogues with better performance and fewer disadvantages in comparison to the original structure. In the past few years, the positive effects of synthetic analogues of curcumin for the treatment of obesity, diabetes and cardiovascular disorders have been reported. In this review, we evaluate the strengths and weaknesses of the reported artificial derivatives and assess their practicality as therapeutic agents.

Topics: Cardiovascular Diseases; Curcumin; Diabetes Mellitus; Humans; Obesity; Quality of Life

Topics: Adipokines; Adiponectin; Adult; Curcuma; Curcumin; Dietary Supplements; Humans; Leptin; Obesity; Randomized Controlled Trials as Topic

Metabolic (dysfunction)-associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease. MAFLD is characterized by the excessive presence of lipids in liver cells and metabolic diseases/dysfunctions, e.g., obesity, diabetes, pre-diabetes, or hypertension. Due to the current lack of effective drug therapy, the potential for non-pharmacological treatments such as diet, supplementation, physical activity, or lifestyle changes is being explored. For the mentioned reason, we reviewed databases to identify studies that used curcumin supplementation or curcumin supplementation together with the use of the aforementioned non-pharmacological therapies. Fourteen papers were included in this meta-analysis. The results indicate that the use of curcumin supplementation or curcumin supplementation together with changes in diet, lifestyle, and/or physical activity led to statistically significant positive changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood insulin (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), and waist circumference (WC). It appears that these therapeutic approaches may be effective in alleviating MAFLD, but more thorough, better designed studies are needed to confirm this.

Topics: Anthropometry; Curcumin; Dietary Supplements; Humans; Non-alcoholic Fatty Liver Disease; Obesity

Obesity is a major cause of morbidity and mortality globally, increasing the risk for chronic diseases. Thus, the need to identify more effective anti-obesity agents has spurred significant interest in the health-promoting properties of natural compounds. Of these, curcumin, the most abundant and bioactive constituent of turmeric, possesses a variety of health benefits including anti-obesity effects. However, despite its anti-obesity potential, curcumin has demonstrated poor bioavailability, which limits its clinical applicability. Synthesizing curcumin derivatives, which are structurally modified analogs of curcumin, has been postulated to improve bioavailability while maintaining therapeutic efficacy. This review summarizes in vitro and in vivo studies that assessed the effects of curcumin derivatives against obesity and its associated metabolic complications. We identified eight synthetic curcumin derivatives that were shown to ameliorate obesity and metabolic dysfunction in diet-induced obese animal models, while five of these derivatives also attenuated obesity and associated metabolic complications in cell culture models. These curcumin derivatives modulated adipogenesis, lipid metabolism, insulin resistance, steatosis, lipotoxicity, inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, fibrosis, and dyslipidemia to a greater extent than curcumin. In conclusion, the findings from this review show that compared to curcumin, synthetic curcumin derivatives present potential candidates for further development as therapeutic agents to modulate obesity and obesity-associated metabolic complications.

Topics: Animals; Apoptosis; Curcumin; Lipid Metabolism; Obesity; Oxidative Stress

Obesity is a global health problem needing urgent research. Synthetic anti-obesity drugs show side effects and variable effectiveness. Thus, there is a tendency to use natural compounds for the management of obesity. There is a considerable body of knowledge, supported by rigorous experimental data, that natural polyphenols, including curcumin, can be an effective and safer alternative for managing obesity. Curcumin is a is an important compound present in

Topics: Clinical Trials as Topic; Curcuma; Curcumin; Energy Metabolism; Health Promotion; Humans; Lipid Metabolism; Medicine, Ayurvedic; Obesity; Weight Loss

Cardiovascular diseases (CVDs) contribute to a large part of worldwide mortality. Similarly, two of the major risk factors for these diseases, aging and obesity, are also global problems. Aging, the gradual decline of body functions, is non-modifiable. Obesity, a modifiable risk factor for CVDs, also predisposes to type 2 diabetes mellitus (T2DM). Moreover, it affects not only the vasculature and the heart but also specific fat depots, which themselves have a major impact on the development and progression of CVDs. Common denominators of aging, obesity, and T2DM include oxidative stress, mitochondrial dysfunction, metabolic abnormalities such as altered lipid profiles and glucose metabolism, and inflammation. Several plant substances such as curcumin, the major active compound in turmeric root, have been used for a long time in traditional medicine and for the treatment of CVDs. Newer mechanistic, animal, and human studies provide evidence that curcumin has pleiotropic effects and attenuates numerous parameters which contribute to an increased risk for CVDs in aging as well as in obesity. Thus, curcumin as a nutraceutical could hold promise in the prevention of CVDs, but more standardized clinical trials are required to fully unravel its potential.

Topics: Animals; Cardiovascular Diseases; Curcumin; Diabetes Mellitus, Type 2; Mitochondria; Obesity; Oxidative Stress

There is growing interest in the health benefits of natural plant pigments such as anthocyanins and curcumin. In this review, we introduce how these pigments can contribute to the prevention of diabetes and obesity by stimulating glucagon-like peptide-1 (GLP-1) secretion or inducing beige adipocyte formation. Of the anthocyanins, delphinidin 3-rutinoside (D3R) was shown to increase GLP-1 secretion. Pre-administered D3R-rich blackcurrant extract (BCE) significantly ameliorated glucose tolerance after intraperitoneal glucose injection in rats by stimulating the secretion of GLP-1 and subsequently inducing insulin secretion. D3R did not break down significantly in the gastrointestinal tract for at least 45-60 min after BCE administration. An increase in endogenous GLP-1 secretion induced by food-derived factors may help to reduce the dosages of diabetic medicines and prevent diabetes. Curcumin has various biological functions, including anti-obesity and anti-diabetic properties. However, high doses of curcumin have been administered in most animal and human trials to date, due mainly to the poor solubility of native curcumin in water and its low oral bioavailability. We demonstrated that a highly dispersible and bioavailable curcumin formulation (HC), but not native curcumin, induces the formation of beige adipocytes. Furthermore, co-administration of HC and artepillin C (a characteristic constituent of Brazilian propolis) at lower doses significantly induces beige adipocyte formation in mice, but administration of the same dose of HC or artepillin C alone does not. Our studies demonstrate that curcumin formulations or the co-administration of curcumin with other food-derived factors provide effects that native curcumin alone does not.

Topics: Adipocytes, Beige; Animals; Anthocyanins; Curcumin; Diabetes Mellitus; Glucagon-Like Peptide 1; Glucose; Humans; Mice; Obesity; Rats; Ribes

The misuse and abuse of antibiotics in livestock and poultry seriously endanger both human health and the continuously healthy development of the livestock and poultry breeding industry. Plant-derived bioactive compounds (curcumin, capsaicin, quercetin, resveratrol, catechin, lignans, etc.) have been widely studied in recent years, due to their extensive pharmacological functions and biological activities, such as anti-inflammatory, antioxidant, antistress, antitumor, antiviral, lowering blood glucose and lipids, and improving insulin sensitivity. Numerous studies have demonstrated that plant-derived bioactive compounds are able to enhance the host's ability to resist or diminish diseases by regulating the abundance of its gut microbiota, achieving great potential as a substitute for antibiotics. Recent developments in both humans and animals have also highlighted the major contribution of gut microbiota to the host's nutrition, metabolism, immunity, and neurological functions. Changes in gut microbiota composition are closely related to the development of obesity and can lead to numerous metabolic diseases. Mounting evidence has also demonstrated that plant-derived bioactive compounds, especially curcumin, can improve intestinal barrier function by regulating intestinal flora. Furthermore, bioactive constituents can be also directly metabolized by intestinal flora and further produce bioactive metabolites by the interaction between the host and intestinal flora. This largely enhances the protective effect of bioactive compounds on the host intestinal and whole body health, indicating that the bidirectional regulation between bioactive compounds and intestinal flora has great application potential in maintaining the host's intestinal health and preventing or treating various diseases. This review mainly summarizes the latest research progress in the bioregulation between gut microbiota and plant-derived bioactive compounds, together with its application potential in humans and animals, so as to provide theoretical support for the application of plant-derived bioactive compounds as new feed additives and potential substitutes for antibiotics in the livestock and poultry breeding industry. Overall, based on this review, it can be concluded that plant-derived bioactive compounds, by modulating gut microbiota, hold great promise toward the healthy development of both humans and animal husbandry.

Topics: Animals; Curcumin; Gastrointestinal Microbiome; Humans; Insulin Resistance; Intestines; Obesity

Oxidative stress and inflammation remain the major complications implicated in the development and progression of metabolic complications, including obesity, type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). In fact, due to their abundant antioxidant and anti-inflammatory properties, there is a general interest in understanding the therapeutic effects of some major food-derived bioactive compounds like curcumin against diverse metabolic diseases. Hence, a systematic search, through prominent online databases such as MEDLINE, Scopus, and Google Scholar was done focusing on randomized controlled trials (RCTs) reporting on the impact of curcumin supplementation in individuals with diverse metabolic complications, including obesity, T2D and NAFLD. Summarized findings suggest that curcumin supplementation can significantly reduce blood glucose and triglycerides levels, including markers of liver function like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2D and NAFLD. Importantly, this effect was consistent with the reduction of predominant markers of oxidative stress and inflammation, such as the levels of malonaldehyde (MDA), tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP) and monocyte chemoattractant protein-1 (MCP-1) in these patients. Although RCTs suggest that curcumin is beneficial in ameliorating some metabolic complications, future research is still necessary to enhance its absorption and bioavailability profile, while also optimizing the most effective therapeutic doses.

Topics: Antioxidants; Biomarkers; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Functional Food; Humans; Inflammation; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress

Obesity remains a pervasive health concern worldwide with concomitant comorbidities such as cardiovascular diseases, diabetes, inflammation, and other metabolic disorders. A wealth of data validates dietary and lifestyle modifications such as restricting caloric intake and increasing physical activity to slow the obesity development. Recently, the advent of phytochemicals such as curcumin, the active ingredient in turmeric, has attracted considerable research interest in tracking down their possible effects in protection against obesity and obesity-related comorbidities. According to the existing literature, curcumin may regulate lipid metabolism and suppress chronic inflammation interacting with white adipose tissue, which plays a central role in the complications associated with obesity. Curcumin also inhibits the differentiation of adipocyte and improves antioxidant properties. In the present review, we sought to deliberate the possible effects of curcumin in downregulating obesity and curtailing the adverse health effects of obesity.

Topics: Adipocytes; Adipose Tissue, White; Curcumin; Humans; Inflammation; Obesity

We conducted a systematic review of human trials examining the effects of dietary phytochemicals on Nrf2 activation. In accordance with the PRISMA guidelines, Medline, Embase and CAB abstracts were searched for articles from inception until March 2020. Studies in adult humans that measured Nrf2 activation (gene or protein expression changes) following ingestion of a phytochemical, either alone or in combination were included. The study was pre-registered on the Prospero database (Registration Number: CRD42020176121). Twenty-nine full-texts were retrieved and reviewed for analysis; of these, eighteen were included in the systematic review. Most of the included participants were healthy, obese or type 2 diabetics. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Twelve different compounds were examined in the included studies: curcumin, resveratrol and sulforaphane were the most common (n = 3 each). Approximately half of the studies reported increases in Nrf2 activation (n = 10); however, many were of poor quality and had an unclear or high risk of bias. There is currently limited evidence that phytochemicals activate Nrf2 in humans. Well controlled human intervention trials are needed to corroborate the findings from in vitro and animal studies.

Topics: Adult; Aged; Antioxidants; Bias; Curcumin; Diabetes Mellitus, Type 2; Humans; Isothiocyanates; Middle Aged; NF-E2-Related Factor 2; Obesity; Oxidative Stress; Phytochemicals; Polyphenols; Resveratrol; Sulfoxides

Non-alcoholic fatty liver disease (NAFLD) is a disorder of excessive fat accumulation in the liver, known as steatosis, without alcohol overconsumption. NAFLD can either manifest as simple steatosis or steatohepatitis, known as non-alcoholic steatohepatitis (NASH), which is accompanied by inflammation and possibly fibrosis. Furthermore, NASH might progress to hepatocellular carcinoma. NAFLD and NASH prevalence is in a continuous state of growth, and by 2018, NAFLD became a devastating metabolic disease with a global pandemic prevalence. The pathophysiology of NAFLD and NASH is not fully elucidated, but is known to involve the complex interplay between different metabolic, environmental, and genetic factors. In addition, unhealthy dietary habits and pre-existing metabolic disturbances together with other risk factors predispose NAFLD development and progression from simple steatosis to steatohepatitis, and eventually to fibrosis. Despite their growing worldwide prevalence, to date, there is no FDA-approved treatment for NAFLD and NASH. Several off-label medications are used to target disease risk factors such as obesity and insulin resistance, and some medications are used for their hepatoprotective effects. Unfortunately, currently used medications are not sufficiently effective, and research is ongoing to investigate the beneficial effects of different drugs and phytochemicals in NASH. In this review article, we outline the different risk factors and pathophysiological mechanisms involved in NAFLD, diagnostic procedures, and currently used management techniques.

Topics: Curcumin; Humans; Insulin Resistance; Liver; Liver Transplantation; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Plant Preparations; Resveratrol; Risk Factors

Over the past decades, the worldwide prevalence of obesity has dramatically increased, thus posing a serious public health threat. Obesity is associated with the development of comorbid conditions and psychological disorders. Several lifestyle interventions have been proposed to tackle obesity; however, long-term maintenance of these interventions often proves challenging. In addition, among the different types of diets there is still a debate about the optimal macronutrient composition that will achieve the best results in weight loss. Recently, several commonly used spices such as pepper, ginger, and curcumin have been shown to play a beneficial role in obesity management. Therefore, exploring the effects of certain herbs or dietary spices on obesity may be promising. Among these spices, curcumin, which is the primary component of the spice turmeric, has gained great interest for its multiple health benefits. Several randomized controlled trials have investigated the potential favorable effects of curcumin supplementation on anthropometric measures. The aim of this review is to evaluate the effect of curcumin supplementation on the anthropometric indices among overweight or obese adults.

Topics: Adult; Anthropometry; Biological Availability; Body Composition; Body Mass Index; Body Weight; Curcumin; Dietary Supplements; Female; Humans; Male; Obesity; Overweight; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Waist Circumference

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.

Topics: Adipogenesis; Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Curcumin; Diet; Dietary Supplements; Endoplasmic Reticulum; Fatty Acids, Unsaturated; Humans; Inflammation; Insulin Resistance; Intestines; Lipids; Macrophages; Obesity; Polyphenols; Resveratrol; Signal Transduction; Thermogenesis

Curcumin is a lipophilic polyphenol, isolated from the plant turmeric of Curcuma longa. Curcuma longa has always been used in traditional medicine in Asian countries because it is believed to have numerous health benefits. Nowadays it is widely used as spice component and in emerging nutraceutical food worldwide. Numerous studies have shown that curcumin possesses, among others, potential anti-inflammatory properties. Obesity represents a main risk factor for several chronic diseases, including type 2 diabetes, cardiovascular disease, and some types of cancer. The establishment of a low-grade chronic inflammation, both systemically and locally in adipose tissue, occurring in obesity most likely represents a main factor in the pathogenesis of chronic diseases. The molecular mechanisms responsible for the onset of the obesity-associated inflammation are different from those involved in the classic inflammatory response caused by infections and involves different signaling pathways. The inflammatory process in obese people is triggered by an inadequate intake of nutrients that produces quantitative and qualitative alterations of adipose tissue lipid content, as well as of various molecules that act as endogenous ligands to activate immune cells. In particular, dysfunctional adipocytes secrete inflammatory cytokines and chemokines, the adipocytokines, able to recruit immune cells into adipose tissue, amplifying the inflammatory response also at systemic level. This review summarizes the most recent studies focused at elucidating the molecular targets of curcumin activity responsible for its anti-inflammatory properties in obesity-associated inflammation and related pathologies.

Topics: Anti-Inflammatory Agents; Curcumin; Humans; Inflammation; Obesity

Curcumin is an active molecule present in turmeric and is the main therapeutic compound. There is growing evidence that curcumin could affect various anthropometric indices. We performed a systematic review to evaluate the efficacy of curcumin supplementation on anthropometric indices in obese and overweight individuals.. A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Google Scholar from inception up to February 2020 to identify randomized controlled trials investigating the effect of curcumin supplementation on anthropometric indices including body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), arm circumference (AC), waist-hip ratio (WHR), total body fat (TBF), and visceral fat (VF) in obese and overweight individuals. The Jadad scale was used to assess the quality of the included studies.. Twenty-eight randomized controlled trials, comprising 2168 participants, were included in the systematic review. The results of 16 papers indicated that curcumin reduced at least one of the anthropometric indices among individuals with a BMI ≥ 25 kg/m. Clinical trials that have independently examined the effects of curcumin in obese or overweight individuals are limited. However, available studies indicate that curcumin has beneficial impacts on various anthropometric indices. Further trials with longer duration of interventions are needed to confirm these findings.

Topics: Body Mass Index; Body Weight; Curcumin; Dietary Supplements; Humans; Obesity; Overweight; Randomized Controlled Trials as Topic

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity; its prevalence is elevating due to the rising epidemic of obesity. Several clinical trials have examined the effects of curcumin supplementation on anthropometric variables in NAFLD patients with inconclusive results. This dose-response meta-analysis aimed to evaluate the impact of curcumin supplementation on body mass index (BMI), body weight, and waist circumference (WC) in patients with NAFLD. A systematic review of the literature was conducted using PubMed/Medline, ISI Web of Science, Scopus, Cochrane Library, EMBASE, Google Scholar, Sid.ir, and Magiran.com to identify eligible studies up to March 2019. A meta-analysis of eligible studies was performed using the random-effects model to estimate the pooled effect size. Eight randomized controlled trials with 520 participants (curcumin group = 265 and placebo group = 255) were included. Supplementation dose and duration ranged from 70 to 3,000 mg/day and 8 to 12 weeks, respectively. Curcumin supplementation significantly reduced BMI (weighted mean difference [WMD] = -0.34 kg/m

Topics: Adult; Anthropometry; Body Mass Index; Body Weight; Curcumin; Dietary Supplements; Female; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Randomized Controlled Trials as Topic; Waist Circumference; Weight Loss

Monocytes and macrophages are important cells of the innate immune system that have diverse functions, including defense against invading pathogens, removal of dead cells by phagocytosis, antigen presentation in the context of MHC class I and class II molecules, and production of various pro-inflammatory cytokines and chemokines such as IL-1β, IL-6, TNF-α and MCP-1. In addition, pro-inflammatory (M1) and anti-inflammatory (M2) macrophages clearly play important roles in the progression of several inflammatory diseases. Therefore, therapies that target macrophage polarization and function by either blocking their trafficking to sites of inflammation, or skewing M1 to M2 phenotype polarization may hold clinical promise in several inflammatory diseases. Dietary-derived polyphenols have potent natural anti-oxidative properties. Within this group of polyphenols, curcumin has been shown to suppress macrophage inflammatory responses. Curcumin significantly reduces co-stimulatory molecules and also inhibits MAPK activation and the translocation of NF-κB p65. Curcumin can also polarize/repolarize macrophages toward the M2 phenotype. Curcumin-treated macrophages have been shown to be highly efficient at antigen capture and endocytosis via the mannose receptor. These novel findings provide new perspectives for the understanding of the immunopharmacological role of curcumin, as well as its therapeutic potential for impacting macrophage polarization and function in the context of inflammation-related disease. However, the precise effects of curcumin on the migration, differentiation, polarization and immunostimulatory functions of macrophages remain unknown. Therefore, in this review, we summarized whether curcumin can influence macrophage polarization, surface molecule expression, cytokine and chemokine production and their underlying pathways in the prevention of inflammatory diseases.

Topics: Alzheimer Disease; Animals; Antigen Presentation; Atherosclerosis; Cell Movement; Cell Polarity; Curcumin; Cytokines; Diet; Humans; Immunologic Factors; Infections; Liver Cirrhosis; Macrophages; Neoplasms; Obesity

Recent controversy regarding the therapeutic potential of curcumin indicates the challenges to research in this field. Here, we highlight the investigations of curcumin and other plant-derived polyphenols that demonstrate their application to metabolic diseases, in particular, obesity and diabetes. Thus, a number of preclinical and clinical investigations have shown the beneficial effect of curcumin (and other dietary polyphenols) in attenuating body weight gain, improving insulin sensitivity, and preventing diabetes development in rodent models and prediabetic subjects. Other intervention studies with dietary polyphenols have also found improvements in insulin resistance. Recent studies suggest that the metabolic effects of curcumin/polyphenols are linked to changes in the gut microbiota. Thus, research into curcumin continues to provide novel insights into metabolic regulation that may ultimately translate into effective therapy.

Topics: Animals; Curcumin; Diabetes Mellitus; Diet; Energy Metabolism; Humans; Insulin Resistance; Obesity; Phytotherapy; Polyphenols; Signal Transduction

Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of

Topics: Antioxidants; Berberine; Curcumin; Dietary Supplements; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Meta-Analysis as Topic; Non-alcoholic Fatty Liver Disease; Obesity; Observational Studies as Topic; Plant Extracts; Probiotics; Randomized Controlled Trials as Topic; Resveratrol; Salvia miltiorrhiza; Silymarin; Ubiquinone; Vitamin D; Vitamin E; Xanthophylls

Obesity in the 21st century society became an important health problem, alarming both the scientists and medicine doctors around the world. That is why, the search for new drug candidates capable to reduce the body weight is of high concern.. This contribution tends to collect current findings on the biochemistry of obesity and on the application of plants and in particular turmeric tuber - a commonly used spice - as an anti-obesity agent.. Following an introduction on the biochemical characteristics of obesity, the description of Curcuma secondary metabolites, their pharmacological applications and a study on the plants' regulatory properties in obesity was summarized. Particular attention was paid to curcumin - the major metabolite present in the extracts of Curcuma spp., which is known to exhibit a variety of pharmacological actions. Also, the characteristics of some semisynthetic analogues of this ferulic acid derivative, characterized by a higher polarity and better bioavailability will be discussed.. Numerous scientific papers treat on the influence of turmeric on weight loss. Additionally, some of them describe its anti-inflammatory properties.. This important spice tends to fight the 21st century plague, which is an excessive weight gain, related to the development of metabolic syndrome, to the occurrence of cardiovascular problems and diabetes, and, in consequence, leading to a significant shortening of life span. As herein proven, the extracts of turmeric play an important role in the regulation of inflammatory reactions which are evoked in the overweight patients, helping them reduce the excess body weight.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Anti-Obesity Agents; Antioxidants; Biological Availability; Biological Products; Curcuma; Curcumin; Humans; Inflammation; Obesity; Plant Extracts; Plant Tubers

Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer.

Topics: Animals; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Humans; Inflammation; Neoplasms; Neurodegenerative Diseases; Obesity

Over the past two decades, obesity has been one of the major public health concerns in most countries. In the search for new molecules that could be used for the treatment of obesity, good perspectives have been opened up for polyphenols, a class of natural bioactive phytochemicals. Experimental and limited clinical trial evidence supports that some polyphenols such as quercetin, curcumin, and resveratrol have potential benefit functions on obesity treatment. This brief review focuses on the main functions of the above-named polyphenols on adipose tissue. These polyphenols may play beneficial effects on adipose tissue under obese condition by alleviating intracellular oxidative stress, reducing chronic low-grade inflammation, inhibiting adipogenesis and lipogenesis, and suppressing the differentiation of preadipocytes to mature adipocytes.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Humans; Mice; Obesity; Quercetin; Rats; Resveratrol; Stilbenes

Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the main component of the Indian spice turmeric, has been used in traditional medicine to improve diabetes and its comorbidities. Since the last two decades, scientific research has shown that in addition to its antioxidant properties, curcumin could also work as protein homeostasis regulator and it is able to modulate other intracellular pathways. Curcumin supplementation has been proposed to improve insulin resistance (IR) through the activation of the insulin receptor and its downstream pathways in several experimental models, pointing out that its clinical use may be a good and innocuous strategy to improve IR-related diseases. IR is associated with many diseases and syndromes like carbohydrate intolerance, diabetes, metabolic syndrome, and cardiovascular disease. Therefore, it is imperative to identify safe therapeutic interventions aimed to reduce side effects that could lead the patient to leave the treatment. To date, many clinical trials have been carried out using turmeric and curcumin to improve metabolic syndrome, carbohydrate intolerance, diabetes, and obesity in individuals with IR. Results so far are inconclusive because dose, time of treatment, and type of curcumin can change the study outcome significantly. However, there is some clinical evidence suggesting a beneficial effect of curcumin on IR. In this review, we discuss the factors that could influence curcumin effects in clinical trials aimed to improve IR and related diseases, and the conclusions that can be drawn from results obtained so far. © 2016 BioFactors, 42(6):561-580, 2016.

Topics: Animals; Antioxidants; Clinical Trials as Topic; Curcumin; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Molecular Targeted Therapy; Obesity; Oxidative Stress; Receptor, Insulin

It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.

Topics: Brain-Derived Neurotrophic Factor; Carbohydrates; Cognition; Cognition Disorders; Curcumin; Diet, High-Fat; Dietary Supplements; Fatty Acids, Omega-3; Hippocampus; Humans; Memory; Memory Disorders; Obesity

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease that is not from excess alcohol consumption, but is often associated with obesity, type 2 diabetes, and metabolic syndrome. NAFLD pathogenesis is complicated and involves oxidative stress, lipotoxicity, mitochondrial damage, insulin resistance, inflammation, and excessive dietary fat intake, which increase hepatic lipid influx and de novo lipogenesis and impair insulin signaling, thus promoting hepatic triglyceride accumulation and ultimately NAFLD. Overproduction of proinflammatory adipokines from adipose tissue also affects hepatic metabolic function. Current NAFLD therapies are limited; thus, much attention has been focused on identification of potential dietary substances from fruits, vegetables, and edible plants to provide a new strategy for NAFLD treatment. Dietary natural compounds, such as carotenoids, omega-3-PUFAs, flavonoids, isothiocyanates, terpenoids, curcumin, and resveratrol, act through a variety of mechanisms to prevent and improve NAFLD. Here, we summarize and briefly discuss the currently known targets and signaling pathways as well as the role of dietary natural compounds that interfere with NAFLD pathogenesis.

Topics: Adipokines; Animals; Carotenoids; Curcumin; Fatty Acids, Omega-3; Fatty Liver; Flavonols; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Polyphenols; Resveratrol; Stilbenes

The prevalence of obesity has steadily increased over the past three decades both in the United States and worldwide. Recent studies have shown the role of dietary polyphenols in the prevention of obesity and obesity-related chronic diseases. Here, we evaluated the impact of commonly consumed polyphenols, including green tea catechins, especially epigallocatechin gallates, resveratrol and curcumin, on obesity and obesity-related inflammation. Cellular studies demonstrated that these dietary polyphenols reduce viability of adipocytes and proliferation of preadipocytes, suppress adipocyte differentiation and triglyceride accumulation, stimulate lipolysis and fatty acid β-oxidation, and reduce inflammation. Concomitantly, the polyphenols modulate signaling pathways including the adenosine-monophosphate-activated protein kinase, peroxisome proliferator activated receptor γ, CCAAT/enhancer binding protein α, peroxisome proliferator activator receptor gamma activator 1-alpha, sirtuin 1, sterol regulatory element binding protein-1c, uncoupling proteins 1 and 2, and nuclear factor-κB that regulate adipogenesis, antioxidant and anti-inflammatory responses. Animal studies strongly suggest that commonly consumed polyphenols described in this review have a pronounced effect on obesity as shown by lower body weight, fat mass and triglycerides through enhancing energy expenditure and fat utilization, and modulating glucose hemostasis. Limited human studies have been conducted in this area and are inconsistent about the antiobesity impact of dietary polyphenols probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), chemical forms of the dietary polyphenols used and confounding factors such as other weight-reducing agents. Future randomized controlled trials are warranted to reconcile the discrepancies between preclinical efficacies and inconclusive clinic outcomes of these polyphenols.

Topics: Adipocytes; Animals; Catechin; Cell Differentiation; Curcumin; Diet; Humans; Obesity; Plant Extracts; Polyphenols; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes; Tea

Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control. Curcumin is an anti-oxidant and nuclear factor kappa-B inhibitor derived from turmeric. A number of studies have shown that dietary curcumin reduces inflammation and delays or prevents obesity-induced insulin resistance and associated complications, including atherosclerosis and immune mediate liver disease. Unfortunately dietary curcumin is poorly absorbed by the digestive system and undergoes glucuronidation and excretion rather than being released into the serum and systemically distributed. This confounds understanding of how dietary curcumin exerts its beneficial effects in type 2 diabetes and associated diseases. New improved methods of delivering curcumin are being developed including nanoparticles and lipid/liposome formulations that increase absorption and bioavailability of curcumin. Development and refinement of these technologies will enable cell-directed targeting of curcumin and improved therapeutic outcome.

Topics: Adipose Tissue; Animals; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Delivery Systems; Humans; I-kappa B Proteins; Inflammation; Insulin; Insulin Resistance; Liver; Liver Diseases; Nanoparticles; NF-kappa B; NF-KappaB Inhibitor alpha; Obesity; Randomized Controlled Trials as Topic

Obesity is characterized as an increased BMI, which is associated with the increased risk of several common cancers, including colorectal, breast, endometrial, renal, esophageal, gallbladder, melanoma, multiple myeloma, leukemia, lymphoma and prostate cancer. The increased risk of obesity-related cancers could be mediated by insulin resistance, adipokines, obesity-related inflammatory cytokines, sex hormones, transcription factors and oxidative stress, which disrupt the balance between cell proliferation and apoptosis. The yellowish compound, curcumin (diferuloylmethane), is known to possess multifaceted pharmacological effects. The molecular mechanisms linking obesity to cancer risk, and how curcumin mediates anticancer and obesity activities, have not yet been publicized. Curcumin modulates multiple molecular targets and reverses insulin resistance as well as other symptoms that are associated with obesity-related cancers. In this study, we show that ample evidence exists to support recommendations that curcumin mediates multiple molecular pathways, and is considered to be of therapeutic value in the treatment and prevention of obesity-related cancers.

Topics: Adipokines; Animals; Antineoplastic Agents; Curcumin; Gonadal Steroid Hormones; Humans; Inflammation Mediators; Insulin; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Lipid Metabolism; Neoplasms; Obesity; Oxidative Stress

A metabolic abnormality such as obesity is a major obstacle in the maintenance of the human health system and causes various chronic diseases including type 2 diabetes, hypertension, cardiovascular diseases, as well as various cancers. This study was designed to summarize the recent scientific knowledge regarding the anti-obesity role of curcumin (diferuloylmethane), which is isolated from the herb curcuma longa, known to possess anti-inflammatory activities. However, little is known about its exact underlying molecular mechanisms in the treatment of obesity and metabolic diseases. Furthermore, cell cultures, animal models of obesity, and few human clinical and epidemiological studies have added the promise for future therapeutic interventions of this dietary compound.. An electronic search was performed using Science finder, Medline, Scopus, Google scholar and collected English language articles from 2000 to 2010, relating to the role of curcumin in obesity and metabolic diseases.. Obesity has been classified as a growing epidemic and its associated metabolic disorders are considered a major risk to the health system. Curcumin interacts with specific proteins in adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells, where it suppresses several cellular proteins such as transcription factor NF-kB, STAT-3, Wnt/β-catenin and activates PPAR-γ, Nrf2 cell signaling pathway. In addition, curcumin downregulates the inflammatory cytokines, resistin and leptin, and upregulates adiponectin as well as other associated proteins. The interactions of curcumin with several signal transduction pathways reverse insulin resistance, hyperglycemia, hyperlipidemia, and other inflammatory symptoms associated with obesity and metabolic diseases.. The modulation of several cellular transduction pathways by curcumin has recently been extended to elucidate the molecular basis for obesity and obesity-related metabolic diseases. These findings might enable novel phytochemical treatment strategies as well as curcumin translation to the clinical practice for the treatment and prevention of obesity-related chronic diseases. Furthermore, the relatively low cost of curcumin, safety and proven efficacy make it advisable to include curcumin as part of healthy diet.

Topics: Adipocytes; Animals; Anti-Inflammatory Agents; Curcuma; Curcumin; Hepatic Stellate Cells; Humans; Metabolic Diseases; Obesity; Pancreas; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic

Extensive research within the past two decades has revealed that obesity, a major risk factor for type 2 diabetes, atherosclerosis, cancer, and other chronic diseases, is a proinflammatory disease. Several spices have been shown to exhibit activity against obesity through antioxidant and anti-inflammatory mechanisms. Among them, curcumin, a yellow pigment derived from the spice turmeric (an essential component of curry powder), has been investigated most extensively as a treatment for obesity and obesity-related metabolic diseases. Curcumin directly interacts with adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells. There, it suppresses the proinflammatory transcription factors nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/beta-catenin, and it activates peroxisome proliferator-activated receptor-gamma and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products. These curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia, and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Dietary Supplements; Humans; Inflammation; Insulin Resistance; Metabolic Syndrome; Obesity

The incidence of obesity is increasing worldwide and is hence considered a major public health concern. Obesity underlies the development of several metabolic complications including cardiovascular diseases, diabetes, and inflammation. Research on ways to slow the development of obesity have traditionally focused on dietary and lifestyle modifications such as restricting caloric intake and increasing physical activity. An area that has recently aroused considerable research interest is investigating the potential role of spices, particularly the Asian spice turmeric, for combating obesity. Curcumin is the active ingredient in turmeric. Evidence suggests curcumin may regulate lipid metabolism, which plays a central role in the development of obesity and its complications. The present review addresses the evidence and mechanisms by which curcumin may play a role in downregulating obesity and reducing the impact of associated problems.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Curcumin; Down-Regulation; Evidence-Based Medicine; Humans; Inflammation; Lipid Metabolism; Obesity

The prevalence of overweight and obesity and their associated metabolic disorders are considered a major threat to the public's health. While several diet and exercise programs are available for weight loss and prevention of weight regain, progress is often slow and disappointing. Recently, natural bioactive phytochemicals present in foods have been discovered for their potential health benefit effects on the prevention of chronic disorders such as cancer, cardiovascular disease, inflammatory and metabolic diseases including obesity. Polyphenols are a class of naturally-occurring phytochemicals, of which some such as catechins, anthocynines, resveratrol and curcumin have been shown to modulate physiological and molecular pathways that are involved in energy metabolism, adiposity, and obesity. The potential in vivo, beneficial effects of these polyphenols on adiposity and obesity as complementary agents in the up-regulation of energy expenditure have emerged by investigating these compounds in cell cultures, animal models of obesity and in some human clinical and epidemiological studies. In this brief review, the efficacy of the above-named polyphenols and their potential efficacy to modulate obesity and some associated disorders are discussed.

Topics: Adipogenesis; Animals; Anthocyanins; Catechin; Cells, Cultured; Curcumin; Diet; Energy Metabolism; Fruit; Humans; Obesity; Polyphenols; Resveratrol; Stilbenes; Tea

It is largely accepted the important role of food and feeding habits on health maintenance and development of non transmissible chronic diseases (NTCD). Epidemiologic evidences show that increasing vegetable consumption positively impacts health. On the other hand, in vivo and in vitro studies in animals show that non-nutrient bioactive food substances partly explain the role of food on the maintenance of health and on the risk reduction of these diseases. The modulation of gene expression of proteins that are involved in the cellular signaling pathways of NTCD is an important mechanism of the bioactive food substances, indicating their importance in disease prevention. Bioavailability, metabolic routes and the action of the resultant metabolites of bioactive food compounds are important aspects that may affect NTCD. All these aspects have actively been investigated in the last years and resulted in a greater understanding of the beginning, progression and prevention of NTCD. This review aimed at discussing the involved mechanisms of the inflammatory response induced by obesity and the role of bioactive food compounds in modulating such response.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biological Availability; Curcumin; Diet; Food Analysis; Humans; Inflammation; Inflammation Mediators; Nutritional Physiological Phenomena; Obesity; Phenols

Topics: Adult; Blood Glucose; Cholesterol; Curcuma; Double-Blind Method; Humans; Hypertension; Inflammation; Insulin Resistance; Metabolic Syndrome; Obesity; Obesity, Abdominal

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to cartilage damage with mostly accompanied by metabolic disorders. This study aimed to investigate the effects of curcumin supplementation on metabolic parameters (lipid profile and glycemic indices), inflammatory factors, visfatin levels, and obesity values in women with RA. This randomized, double-blind, placebo-controlled clinical trial was conducted on 48 women with RA. The patients were treated with curcumin (500 mg once a day) or placebo for 8 weeks. Fasting blood samples, anthropometric measurements, dietary intakes, and physical activity levels of subjects were collected at baseline and the end of the study. Curcumin supplementation significantly decreased homeostatic model assessment for insulin resistance (HOMA-IR), erythrocyte sedimentation rate, serum levels of high-sensitivity C-reactive protein and triglycerides, weight, body mass index, and waist circumference of patients compared with the placebo at the end of the study (p < .05 for all). HOMA-IR and triglyceride levels significantly increased within the placebo group. Changes in fasting blood sugar, insulin, other lipids profile, and visfatin levels were not significant in any of the groups (p > .05). These results support the consumption of curcumin, as a part of an integrated approach to modulate metabolic factors, inflammation, and adiposity in women with RA.

Topics: Arthritis, Rheumatoid; Blood Glucose; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Male; Nicotinamide Phosphoribosyltransferase; Obesity

The present study aimed to investigate the effects of nano-curcumin supplementation on adipokines levels and clinical signs in obese and overweight patients with migraine.. Forty-four patients with episodic migraine participated in this clinical trial and were divided into two groups nano-curcumin (80 mg/day) and the control group over 2-month period. At the baseline and the end of the research, the serum levels of MCP-1, Resistin, and Visfatin were measured using the ELISA method. In addition, the headache attack frequencies, severity, and duration of pain were recorded. The results of the present study showed that nano-curcumin can significantly reduce MCP-1 serum levels in the nano-curcumin supplemented group (P = 0.015, size effect = 13.4%). In the case of resistin and visfatin, nano-curcumin supplementation exerted no statistically significant changes in serum levels (P > 0.05). Nano-curcumin also significantly reduced the attack frequencies, severity, and duration of headaches (P < 0.05). These findings indicate that targeting curcumin can be a promising approach to migraine management. However, further comprehensive human trials are needed to confirm these findings.. This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20160626028637N2 on the date 2020-07-10.

Topics: Adipokines; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Iran; Migraine Disorders; Nicotinamide Phosphoribosyltransferase; Obesity; Overweight; Resistin

To evaluate the effect of curcumin treatment on hepatic fat content in obese individuals.. In a double-blind, parallel-group trial, 37 obese, non-diabetic individuals were randomized to placebo or curcumin treatment for 6 weeks. Curcumin was dosed as lecithin-formulated tablet; 200 mg twice daily. The primary endpoint was hepatic fat content as assessed by magnetic resonance spectroscopy (MRS). Other endpoints included anthropometric measurements, hepatic biomarkers including FibroScan measurements, metabolic variables, inflammation markers, appetite measures and ad libitum food intake.. Compared with placebo, curcumin treatment for 6 weeks had no significant effect on MRS-assessed hepatic fat content in obese individuals with primarily mild steatosis. Curcumin was well tolerated.

Topics: Adult; Blood Glucose; Curcumin; Double-Blind Method; gamma-Glutamyltransferase; Humans; Lecithins; Middle Aged; Obesity; Triglycerides

Management of prediabetes is a critical step to prevent type-2 diabetes. Curcumin and zinc have been studied as an antioxidant, antiinflammatory, and antidiabetic agents. In this clinical trial, 84 subjects were randomized into curcumin (500 mg), zinc (30 mg), zinc and curcumin, and placebo groups for 90 days. At the baseline and the end of the study, the outcomes (fasting plasma glucose (FPG), 2-hour postprandial glucose (2hpp), HbA

Topics: Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Diet, Reducing; Dietary Supplements; Double-Blind Method; Humans; Insulin; Insulin Resistance; Obesity; Overweight; Prediabetic State; Zinc

Chronic conditions such as obesity, which contribute to endothelial dysfunction in older adults, can cause impairments in cerebrovascular perfusion, which is associated with accelerated cognitive decline. Supplementing the diet with bioactive nutrients that can enhance endothelial function, such as fish oil or curcumin, may help to counteract cerebrovascular dysfunction.. Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention.. ACTRN12616000732482p.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Blood Pressure; C-Reactive Protein; Cardiovascular System; Cerebrovascular Circulation; Curcumin; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Fish Oils; Health Status; Heart Rate; Humans; Inflammation Mediators; Lipids; Male; Middle Aged; New South Wales; Obesity; Time Factors; Treatment Outcome; Vascular Stiffness

Curcumin has previously been shown to enhance mood in non-depressed older adults. However, observed benefits were limited to short-term supplementation (4 weeks). In a 16 week randomized, double-blind, placebo-controlled, 2 × 2 factorial design trial, we supplemented overweight or obese non-depressed adults (50-80 years) with curcumin (160 mg/day), fish oil (2000 mg docosahexaenoic acid +400 mg eicosapentaenoic acid/day), or a combination of both. Secondary outcomes included mental wellbeing measures (mood states and subjective memory complaints (SMCs)) and quality of life (QoL). Furthermore, plasma apolipoprotein E4 (APOE4) was measured to determine whether APOE4 status influences responses to fish oil. Curcumin improved vigour (

Topics: Affect; Aged; Apolipoprotein E4; Curcumin; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Fish Oils; Humans; Male; Memory; Mental Health; Middle Aged; New South Wales; Obesity; Overweight; Quality of Life

The prevalence of prediabetes is increasing worldwide. Unfortunately, prediabetes is related to non-communicable diseases. A high risk of developing type 2 diabetes mellitus (T2DM) is reported in people with prediabetes. Curcumin, a polyphenol, might lead to its therapeutic role in obesity and some obesity-related metabolic diseases. Zinc is a trace element that plays a key role in the synthesis and action of insulin, carbohydrate metabolism, and decreasing inflammation. There has been no clinical trial of zinc and curcumin co-supplementation in patients with prediabetes. In previous studies, the single administration of zinc or curcumin has not been conducted on many of the studied markers in prediabetic patients.. The purpose of this randomized double-blind placebo-controlled clinical trial is to investigate the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers among 84 prediabetic patients with body mass index (BMI) between 25 and 35. Also, liver enzyme, serum zinc, urine zinc, blood pressure, anthropometric parameters, quality of life, adherence to co-supplementation, the side effects of co-supplementation, physical activity, and dietary intake will be assessed. Women or men (18-50 years old for men and 18 years to before menopause for women) will be followed for 3 months (90 days). This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences.. A diet rich in antioxidants, polyphenols, and phytochemicals has been shown to have a beneficial role in prediabetes. According to the beneficial properties of curcumin or zinc and inadequate evidence, RCTs are needed to assess the effect of curcumin and zinc co-supplementation in native prediabetes patients. We hope the results of the present trial, negative or positive, fill this gap in the literature and facilitate the approach for a much larger, multi-center clinical trial. In conclusion, a synergic effect of co-supplementation along with a weight-loss diet may delay the progression to type 2 diabetes mellitus.. Iranian Registry of Clinical Trials (IRCT) IRCT20190902044671N1 . Registered on 11 October 2019.

Topics: Adolescent; Adult; Antioxidants; Biomarkers; Blood Glucose; Clinical Trials, Phase II as Topic; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Lipids; Male; Middle Aged; Obesity; Overweight; Prediabetic State; Quality of Life; Randomized Controlled Trials as Topic; Young Adult; Zinc

The aim of the current study was to assess the effects of curcumin supplementation on glycemic status, lipid profile and high sensitivity C-reactive protein (hs-CRP) serum levels in women with polycystic ovary syndrome (PCOS).. This randomized double-blind placebo-controlled clinical trial was conducted on 60 women who were randomly assigned to the intervention or control groups using block randomization.. Infertility referral center.. Curcumin (500 mg/d) or placebo twice daily for 6 weeks.. Serum evaluation of lipid profile (triglycerides (TG), low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol concentrations, LDL/HDL-C and TG/HDL-C ratios), glycemic index (fasting blood sugar (FBS), insulin concentrations, homeostasis model of assessment insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)) and hs-CRP levels.. Glycemic index, lipid profile and hs-CRP serum levels were measured at first and at the end of trial. Serum insulin (p = 0.020) and Quantitative Insulin Sensitivity Check Index (QUICKI) (p = 0.003) were improved significantly, while Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (p = 0.067) improved marginally in curcumin treated group (within group analysis).. Curcumin supplementation might be beneficial for improving serum insulin and QUICKI, however, future investigations are suggested in order to draw a firm link between curcumin and glycemia control.

Topics: Adult; C-Reactive Protein; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Hyperinsulinism; Hyperlipidemias; Obesity; Overweight; Polycystic Ovary Syndrome

This study aimed to determine whether an enhanced bioavailable curcumin formulation, CurQfen®, would improve circulating cardiovascular disease-related blood biomarkers and arterial function in young (age 18-35 y), obese (body mass index ≥ 30.0 kg/m. This double-blinded, placebo-controlled trial evaluated 22 men. The participants were matched based on body mass index and randomized to the intervention (curcumin formulated with fenugreek soluble fiber, for enhanced absorption) or control (fenugreek soluble fiber) group for 12 wk at 500mg/d without dietary modification or exercise. Blood samples and endothelial function measures were acquired at 0 and 12 wk, and blood samples were analyzed for cardiovascular disease-related blood biomarkers. Furthermore, central (aortic) blood pressure and augmentation index were monitored at 0, 4, 8, and 12 wk.. After 12 wk of intervention, homocysteine levels were lower (curcumin before: 12.22 ± 2.29 µg/mL, after: 8.62 ± 1.02 µg/mL versus placebo before: 9.45 ± 0.84 µg/mL, after: 11.84 ± 1.63 µg/mL; P = 0.04) and high-density lipoprotein levels were higher (curcumin before: 40.77 ± 5.37 mg/dL, after: 54.56 ± 11.72 mg/dL versus placebo before: 61.20 ± 5.76 mg/dL, after: 48.82 ± 5.49 mg/dL; P = 0.04) in the curcumin group relative to the placebo group. However, there was no significant difference in changes between the circulating concentrations of glucose, insulin, leptin, adiponectin, or oxidative stress biomarkers in the curcumin group compared with the placebo group (P > 0.05). No changes were found with endothelial function, augmentation index, or central blood pressure in the curcumin group compared with the placebo group (P > 0.05).. Our data provide evidence for an enhanced bioavailable curcumin to improve homocysteine and high-density lipoprotein concentrations, which may promote favorable cardiovascular health in young, obese men. Improvements in endothelial function or blood pressure were not observed with curcumin supplementation, thus further investigation is warranted.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Arteries; Biomarkers; Cardiovascular Diseases; Curcumin; Dietary Supplements; Double-Blind Method; Endothelium, Vascular; Homocysteine; Humans; Lipoproteins; Male; Obesity; Risk Factors; Young Adult

It is well known that there is a strong linkage between obesity, systemic low-grade inflammation, and oxidative stress in the pediatric population. Possible strategies that might control obesity and its relevant problems in this crucial group are of utmost importance. Therefore, the aim of this study was to evaluate the effects of curcumin supplements on inflammation, oxidative stress, and chemerin levels in adolescent girls.. Totally, 60 overweight and obese adolescent girls were randomly assigned to either placebo or intervention group in a randomized placebo-controlled parallel trial design. Adolescents consumed one 500-mg curcumin or placebo per day along with a slight weight loss diet for 10 weeks. High-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), total antioxidant capacity (TAC), malondialdehyde (MDA), chemerin levels, and anthropometric measurements were assessed at the beginning and end of the trial.. Curcumin supplementation had a significant effect on IL-6 levels and oxidative stress markers including TAC and MDA in crude model. After controlling the effects of confounders, curcumin supplementation had a substantial effect on inflammation (hs-CRP and IL-6) and oxidative stress (TAC) marker of adolescents.. Ten weeks of curcumin supplementation had beneficial effects on inflammation and oxidative stress markers among postpubescent overweight and obese girl adolescents.

Topics: Adolescent; Curcumin; Female; Humans; Inflammation; Obesity; Overweight; Oxidative Stress

Different studies have been conducted on the role of curcumin in health since having multiple properties, including antioxidant and anti-inflammatory effects. Due to the lack of studies regarding curcumin effects on obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory indices, insulin resistance and liver function, especially by nesfatin.. This trial will be conducted in the Oil Company central hospital of Tehran, Iran with a primary level of care.. 84 obese patients with NAFLD diagnosed using ultrasonography will be employed according to the eligibility criteria‎.. The patients will be randomly divided into two equal groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3 months, follow-up monthly). Also, lifestyle changes (low-calorie diet and physical activity) will be advised.. A general questionnaire, 24 hours food recall (at the beginning, middle and end) and short-form International Physical Activity Questionnaire will be completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood sugar and insulin, insulin resistance and sensitivity and glycosylated haemoglobin), lipids (triglyceride, total cholesterol and low-density and high-density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high-sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function (alanine and aspartate transaminase) and nesfatin will be measured at the beginning and end of the study.. This trial would be the first experiment to determine nanocurcumin efficacy on certain blood factors among obese patients with NAFLD. Nevertheless, studying the potential consequences of curcumin in various diseases, especially NAFLD, is required for clinical use.. IRCT2016071915536N3; pre-results.

Topics: Adult; Body Mass Index; Curcumin; Dietary Supplements; Exercise; Female; Humans; Insulin; Insulin Resistance; Iran; Lipids; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Research Design

To investigate the effectiveness of curcumin, a natural polyphenolic compound with antioxidant and anti-inflammatory activities, on the frequency of symptoms of anxiety and depression in obese individuals.. In this double blind, cross-over trial, 30 obese subjects were randomized to receive either curcumin (1 g/day) or placebo for a period of 30 days. Following a wash-out interval of 2 weeks, each subject was crossed over to the alternative regimen for a further 30 days. Severity of anxiety and depression was assessed at baseline and at weeks 4, 6 and 10 of the trial using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) scales, respectively.. Mean BAI score was found to be significantly reduced following curcumin therapy (P=0.03). However, curcumin supplementation did not exert any significant impact on BDI scores (P=0.7).. Curcumin has a potential anti-anxiety effect in individuals with obesity.

Topics: Adult; Anxiety; Curcumin; Demography; Depression; Female; Humans; Male; Obesity; Placebos; Psychiatric Status Rating Scales

We evaluated the effects of curcumin treatment on protein oxidation (PO), lipid peroxidation (LP) and brain-derived neurotrophic factor (BDNF) levels in the hippocampus and frontal cortex (FC) of diabetic db/db mice (DM) and in sera of obese humans. Thus, DM were treated daily with 50 mg/kg of curcumin during an 8-week period. Obese human were treated daily with 500 and 750 mg of curcumin that was administered orally for 12 weeks; BDNF, PO and LP levels in sera were determined at in weeks 0, 2, 6 and 12 of treatment. BDNF levels decreased in hippocampus and FC of DM as compared with untreated wild-type mice. Curcumin improved or restored BDNF levels to normal levels in DM, but curcumin did not have any effect on BDNF levels in sera of obese humans. In hippocampus and FC of DM, hyperglycaemia and curcumin did not have effect on LP levels. Hyperglycaemia increased PO levels in hippocampus and FC, whereas curcumin decreased these levels in hippocampus but not in FC. In sera of obese humans, the 500-mg dose decreased LP levels in weeks 6 and 12 when compared with basal levels, but the 750-mg dose did not have any effect; both doses of curcumin decreased PO levels in weeks 2, 6 and 12 of treatment when compared with basal levels. Present results suggest a therapeutic potential of curcumin to decrease oxidation caused by obesity in humans and also show that curcumin restores BDNF levels in DM.

Topics: Adult; Animals; Brain-Derived Neurotrophic Factor; Curcumin; Diabetes Mellitus; Diabetes Mellitus, Experimental; Humans; Male; Mice; Obesity; Oxidative Stress; Single-Blind Method

Obesity is a disorder often accompanied by a heightened state of systemic inflammation and immunoactivation. The present randomized crossover trial aimed to investigate the efficacy of curcumin, a bioactive polyphenol with established anti-inflammatory and immunomodulatory effects, on the serum levels of a panel of cytokines and mediators in obese individuals.. Thirty obese individuals were randomized to receive curcumin at a daily dose of 1 g or a matched placebo for 4 weeks. Following a 2-week wash-out period, each group was assigned to the alternate treatment regimen for another 4 weeks. Serum samples were collected at the start and end of each study period. Serum levels of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFNγ, EGF, MCP-1, and TNF α were measured using a multiplex Biochip Array Technology based method.. Mean serum IL-1β (P = 0.042), IL-4 (P = 0.008), and VEGF (P = 0.01) were found to be significantly reduced by curcumin therapy. In contrast, no significant difference was observed in the concentrations of IL-2, IL-6, IL-8, IL-10, IFNγ, EGF, and MCP-1.. The findings of the present trial suggested that curcumin may exert immunomodulatory effects via altering the circulating concentrations of IL-1β, IL-4, and VEGF.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Curcumin; Cytokines; Drug Combinations; Humans; Immunologic Factors; Middle Aged; Obesity; Treatment Outcome; Young Adult

Whether supplementation of curcuminoids decreases serum adipocyte-fatty acid binding protein (A-FABP) level and whether this decrease benefits glucose control is unclear. One-hundred participants (n=50 administered curcuminoids, n=50 administered placebo) from our previous report on the effect of curcuminoids on type 2 diabetes in a 3-month intervention were assessed for levels of serum A-FABP, oxidative stress, and inflammatory biomarkers. Curcuminoids supplementation led to significant decreases in serum A-FABP, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 levels. Curcuminoids supplementation also significantly increased serum superoxide dismutase (SOD) activity. The change in serum A-FABP levels showed positive correlations with changes in levels of glucose, free fatty acids (FFAs), and CRP in subjects supplemented with curcuminoids. Further stepwise regression analysis showed that A-FABP was an independent predictor for levels of FFAs, SOD, and CRP. These results suggest that curcuminoids may exert anti-diabetic effects, at least in part, by reductions in serum A-FABP level. A-FABP reduction is associated with improved metabolic parameters in human type 2 diabetes.

Topics: Biomarkers; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Fatty Acid-Binding Proteins; Humans; Hypoglycemic Agents; Obesity; Oxidative Stress; Treatment Outcome

Curcuminoids have potentially important functional qualities including anti-inflammatory and antioxidant properties. In this randomized double-blind placebo-controlled cross-over trial, the effects of a curcuminoid supplement on serum pro-oxidant-antioxidant balance (PAB) and antibody titres to Hsp27 (anti-Hsp27) and oxLDL (anti-oxLDL) were investigated. Thirty obese individuals were randomized to receive either curcuminoids (1 g/day) or placebo for a period of 30 days. After a wash-out period of 2 weeks, subjects were crossed over to the alternate regimen for another 30 days. Serum PAB along with anti-Hsp27 and anti-oxLDL titres was measured at the beginning and at the end of each study period. There was no significant carry-over effect for any of the assessed parameters. Curcuminoid supplementation was associated with a significant decrease in PAB (p = 0.044). However, no significant change was observed in serum concentrations of anti-Hsp27 or anti-oxLDL (p > 0.05). These findings suggest that oral curcuminoids supplementation (1g/day) is effective in reducing oxidative stress burden, though this needs to be validated in larger study populations.

Topics: Adult; Antibodies; Antioxidants; Cross-Over Studies; Curcumin; Dietary Supplements; Double-Blind Method; Female; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Humans; Lipoproteins, LDL; Male; Middle Aged; Molecular Chaperones; Obesity; Oxidants; Oxidative Stress; Reactive Oxygen Species

Dyslipidemia is a leading risk factor for cardiovascular disease and is also a common feature of obesity. Curcumin is a bioactive phytochemical with well-known antioxidant, anti-inflammatory, and cardioprotective properties. The present study investigated the hypolipidemic activity of curcumin in obese individuals. Participants (n = 30) were treated with curcuminoids (1 g/day), or placebo in a randomized, double-blind, placebo-controlled, crossover trial. Serum concentrations of total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, together with anthropometric parameters and high-sensitivity C-reactive protein were measured before and after each treatment period. Anthropometric parameters including weight, BMI, waist circumference, hip circumference, arm circumference, and body fat remained statistically unchanged by the end of trial (p > 0.05). As for the lipid profile parameters, serum triglycerides were significantly reduced following curcumin supplementation (p = 0.009). However, curcuminoids were not found to affect serum levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (p > 0.05). In summary, the findings of the present study indicated that curcuminoid supplementation (1 g/day for 30 days) leads to a significant reduction in serum triglycerides concentrations but do not have a significant influence on other lipid profile parameters as well as body mass index and body fat.

Topics: Adolescent; Adult; Anthropometry; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Curcumin; Dietary Supplements; Double-Blind Method; Dyslipidemias; Female; Humans; Male; Middle Aged; Obesity; Triglycerides; Young Adult

We previously found that curcuminoids decreased blood glucose and improved insulin resistance by reducing serum free fatty acids (FFAs) and increasing fatty acid oxidation in skeletal muscle of diabetic rats. This study was to investigate whether curcuminoids have beneficial effects on type 2 diabetic patients, and its possible mechanisms.. Overweight/obese type 2 diabetic patients (BMI ≥ 24.0; fasting blood glucose ≥ 7.0 mmol/L or postprandial blood glucose ≥11.1 mmol/L) were randomly assigned to curcuminoids (300 mg/day) or placebo for 3 months. Bodyweight, glycosylated hemoglobin A1c (HbA1c ,% ), serum fasting glucose, FFAs, lipids, and lipoprotein lipase (LPL) were determined. A total of 100 patients (curcuminoids, n = 50; placebo, n = 50) completed the trial. Curcuminoids supplementation significantly decreased fasting blood glucose (p < 0.01), HbA1c (p = 0.031), and insulin resistance index (HOMA-IR) (p < 0.01) in type 2 diabetic patients. Curcuminoids also led to a significant decrease in serum total FFAs (p < 0.01), triglycerides (P = 0.018), an increase in LPL activity (p < 0.01).. These findings suggest a glucose-lowering effect of curcuminoids in type 2 diabetes, which is partially due to decrease in serum FFAs, which may result from promoting fatty acid oxidation and utilization.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipoprotein Lipase; Male; Middle Aged; Obesity; Postprandial Period; Triglycerides; Young Adult

Among obesity-associated disorders, low-grade inflammation has been described. The putative therapeutic properties of citrus and curcumin polyphenols could be associated with their anti-inflammatory properties. Two diets supplemented either with hesperidin (0.05 %) and naringin (0.1 %) from citrus extract or with highly bioavailable curcumin from Curcuma longa extract (0.09 %) were fed to eight obese cats for two 8-week periods (cross-over study design) while maintaining animals in an obese state. Plasma acute-phase protein (APP; α1-acid glycoprotein (AGP), serum amyloid A and haptoglobin) levels were assessed before and at the end of each test period. TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12, IL-18, transforming growth factor-β, interferon (IFN)-γ mRNA levels were determined in peripheral blood mononuclear cells (PBMC) by real-time PCR. Compared with pre-study values, supplementation with citrus polyphenols resulted in lower plasma AGP and haptoglobin concentrations, while that with curcumin resulted in lower plasma AGP concentration. There were no differences between the supplementations. TNF-α, IL-1β, IL-4, IL-5, IL-10, IL-12, IL-18, transforming growth factor-β, mRNA levels remained unaffected by either dietary supplementation. In contrast, IFN-γ and IL-2 mRNA levels were lower at the end of the citrus and the curcumin supplementation, respectively. There were no differences between the supplementations. The present study results show a slight effect of citrus and curcumin supplementation on inflammatory markers expressed by PBMC, and a decreased concentration of APP, which are mainly expressed by the liver. This would confirm that hesperidin and naringin or highly bioavailable curcumin extract have beneficial effects, targeted in the liver and could improve the obesity-related inflammatory state.

Topics: Acute-Phase Proteins; Animals; Cat Diseases; Cats; Citrus; Cross-Over Studies; Curcumin; Cytokines; Female; Flavanones; Gene Expression Regulation; Hesperidin; Inflammation; Leukocytes, Mononuclear; Male; Obesity; RNA, Messenger

Maternal obesity and dietary style in the pregnancy-lactation period may result in long-term effects on the metabolic health of the offspring, thus increasing the risk of diseases, such as obesity, diabetes, and cardiovascular diseases. Curcumin is a natural polyphenolic compound that has beneficial properties on metabolism. Accordingly, this study is intended to evaluate the effects of curcumin supplementation in pregnant and lactating female mice on the anthropometric, metabolic and molecular parameters of the offspring fed a hyperglycemic diet. The study was conducted with 24 male mice randomized into three groups: i) control group (SD) originating from dams fed a standard diet; ii) hyperglycemic group (HGD) originating from dams fed a hyperglycemic diet; iii) curcumin group (CUR) originating from dams fed a hyperglycemic diet and supplemented with curcumin in the pregnancy-lactation period. All offspring groups were fed a hyperglycemic diet for 12 weeks. Anthropometricand biochemical parameters were measured, as well as the expression of thermogenesis-associated markers in the interscapular brown and inguinal white adipose tissues. The results showed less weight gain in the CUR group, with a concomitant reduction in food consumption compared to the HGD group. Biochemical parameters indicated lower levels of total cholesterol, glucose, and insulin for the CUR group, in addition to improved glucose tolerance and insulin sensitivity. The molecular evaluation indicated increased mRNA expression levels of UCP1 and PRDM16 in the brown and white adipose tissues. It is concluded that curcumin supplementation in the pregnancy-lactation period in dams with diet-induced obesity may lead to improvements in the offspring's metabolic phenotype, even if they are submitted to an obesogenic environment, possibly via thermogenesis activation.

Topics: Adipose Tissue; Animals; Curcumin; Diet, High-Fat; Female; Glucose; Humans; Lactation; Male; Mice; Obesity; Pregnancy; Thermogenesis

Cachexia is a multifactorial debilitating syndrome that is responsible for 22% of mortality among cancer patients, and there are no effective therapeutic agents available. Curcumin, a polyphenolic compound derived from the plant turmeric, has been shown to have anti-inflammatory, antioxidant, anti-autophagic, and antitumor activities. However, its function in cancer cachexia remains largely unexplored.. This study aimed to elucidate the mechanisms by which curcumin improves adipose atrophy in cancer cachexia.. C26 tumor-bearing BALB/c mice and β3-adrenoceptor agonist CL316243 stimulated BALB/c mice were used to observe the therapeutic effects of curcumin on the lipid degradation of cancer cachexia in vivo. The effects of curcumin in vitro were examined using mature 3T3-L1 adipocytes treated with a conditioned medium of C26 tumor cells or CL316243.. Mice with C26 tumors and cachexia were protected from weight loss and adipose atrophy by curcumin (50 mg/kg, i.g.). Curcumin significantly reduced serum levels of free fatty acids and increased triglyceride levels. In addition, curcumin significantly inhibited PKA and CREB activation in the adipose tissue of cancer cachectic mice. Curcumin also ameliorated CL316243-induced adipose atrophy and inhibited hormone-mediated PKA and CREB activation in mice. Moreover, the lipid droplet degradation induced by C26 tumor cell conditioned medium in mature 3T3-L1 adipocytes was ameliorated by curcumin (20 µM) treatment. Curcumin also improved the lipid droplet degradation of mature 3T3-L1 adipocytes induced by CL316243.. Curcumin might be expected to be a therapeutic supplement for cancer cachexia patients, primarily through inhibiting adipose tissue loss via the cAMP/PKA/CREB signaling pathway.

Topics: Animals; Atrophy; Cachexia; Culture Media, Conditioned; Curcumin; Lipolysis; Mice; Neoplasms; Obesity; Signal Transduction

Glucagon-like peptide-1 (GLP-1) deficiency occurs in obesity-related pathologies due to defects in the intestinal lumen. And expanding the L-cell population has emerged as a promising avenue to elevate GLP-1 secretion to tackle metabolic disorders. Curcumin (Cur), the principal active component of spice turmeric, possesses well-established anti-obesity properties. To clarify, the study investigates whether Cur promotes GLP-1 secretion built upon the L-cell expansion.. The findings suggest that Cur may act as a natural TGR5 agonist and FXR antagonist to improve obesity by enhancing GLP-1 release from L-cell expansion via the gut microbiota-BAs-TGR5/FXR axis, and it may serve as a promising therapeutic agent to compensate obesity-related metabolic disorders.

Topics: Animals; Bile Acids and Salts; Curcumin; Glucagon-Like Peptide 1; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Microbiota; Obesity; Receptors, G-Protein-Coupled

Obesity is a non-communicable chronic disease that continues to increase around the world. Recently, it has been shown that curcumin positively affects lipid, energy metabolism, and body weight change. Moreover, polyamines are aliphatic polycations, which can be found in all mammalian cells and foods and have been shown to prevent obesity through many different mechanisms. However, whether the co-administration of curcumin and polyamines has synergistic effects has yet to be clarified. Our study aimed to examine the effects of curcumin and polyamines on obesity and to assess the changes in serum polyamine levels and tissue parameters. 28 Sprague-Dawley male rats were fed a high-fat diet for 10 weeks to develop obesity, and then they were randomly divided into 4 groups as the control group (CONT), curcumin group (CUR), polyamine group (POL), curcumin and polyamine group (CUR+POL) and supplements were administered for 6 weeks. As a result, the lowest feed consumption in rats was recorded in the CUR+POL group, and the group with the lowest weight after supplements was the POL group, then the CUR+POL, CONT, and CUR groups, respectively. N-acetyl putrescine and GABA levels increased significantly after obesity development. The total histopathological score in fat, liver, and kidney tissues increased significantly in the CONT group. In the CUR+POL group, damage to the tissues was in the direction of recovery compared to the other groups, and the expression of NF-κB was significantly low. These results suggest that combined curcumin and polyamines may have protective effects.

Topics: Animals; Curcumin; Diet, High-Fat; Male; Mammals; Obesity; Polyamines; Rats; Rats, Sprague-Dawley

The prevalence of obesity has increased, with excessive consumption of high-fat foods being one of the primary causes. Curcumin, a polyphenol extracted from Curcuma longa L., exhibits anti-inflammatory activity.  The study aims to investigate the effects of curcumin supplementation in different doses on the biochemical profile, inflammatory response, and gut microbiota profile in mice that are fed with high-fat diet (HFD).. C57BL/6 male mice are fed a standard diet, or a HFD with or without different doses of curcumin (50, 250, and 500 mg kg. The findings suggest that curcumin has the potential to improve the inflammatory response and modulate healthy gut microbiota. Further studies are needed to clarify the role of curcumin as a preventive and effective strategy for obesity.

Topics: Animals; Body Weight; Curcumin; Diet, High-Fat; Dietary Supplements; Gastrointestinal Microbiome; Interleukin-10; Male; Mice; Mice, Inbred C57BL; Obesity

Although aging is a physiological process to which all organisms are subject, the presence of obesity and type 2 diabetes accelerates biological aging. Recent studies have demonstrated the causal relationships between dietary interventions suppressing obesity and type 2 diabetes and delaying the onset of age-related endocrine changes. Curcumin, a natural antioxidant, has putative therapeutic properties such as improving insulin sensitivity in obese mice. However, how curcumin contributes to maintaining insulin homeostasis in aged organisms largely remains unclear. Thus, the objective of this study is to examine the pleiotropic effect of dietary curcumin on insulin homeostasis in a diet-induced obese (DIO) aged mouse model. Aged (18-20 months old) male mice given a high-fat high-sugar diet supplemented with 0.4% (w/w) curcumin (equivalent to 2 g/day for a 60 kg adult) displayed a different metabolic phenotype compared to mice given a high-fat high-sugar diet alone. Furthermore, curcumin supplementation altered hepatic gene expression profiling, especially insulin signaling and senescence pathways. We then mechanistically investigated how curcumin functions to fine-tune insulin sensitivity. We found that curcumin supplementation increased hepatic insulin-degrading enzyme (IDE) expression levels and preserved islet integrity, both outcomes that are beneficial to preserving good health with age. Our findings suggest that the multifaceted therapeutic potential of curcumin can be used as a protective agent for age-induced metabolic diseases.

Topics: Aging; Animals; Body Composition; Curcumin; Diet, High-Fat; Dietary Sugars; Gene Expression Regulation; Homeostasis; Insulin; Male; Mice; Obesity; Random Allocation

We aimed to identify the molecular mechanisms behind curcumin's therapeutic benefits for metabolic syndrome (MetS) and its components.. The Comparative Toxicogenomics Database, MIENTURNET, Metascape, GeneMania, and Cytoscape software were critical analytic tools.. Curcumin may have therapeutic effects on MetS and its components via the following genes: NOS3, IL6, INS, and ADIPOQ, particularly PPARG. Curcumin has higher docking scores than other genes with INS and PPARG (docking scores: -8.3 and -5.8, respectively). Physical interactions (56%) were found to be the most prevalent for dyslipidemia, co-expression for hypertension, obesity, T2DM, and MetS. "Galanin receptor pathway", "lipid particles composition", "IL-18 signaling pathway", "response to extracellular stimulus", and "insulin resistance" were listed in the first of the key pathways for MetS, dyslipidemia, hypertension, obesity, and diabetes, respectively. The protein-protein interaction enrichment analysis study also identified "vitamin B12 metabolism," "folate metabolism," and "selenium micronutrient network" as three major molecular pathways linked to MetS targeted by curcumin. PPARG was the key transcription factor that regulated practically all curcumin-targeted genes linked to MetS and its components. Curcumin targeted hsa-miR-155-5p, which has been linked to T2DM, hypertension, and MetS, as well as hsa-miR-130b-3p and hsa-miR-22-3p, which have been linked to dyslipidemia and obesity, respectively. In silico, sponges that regulated hsa-miR-155-5p were developed and evaluated. Curcumin, MetS, and its components have been found to target adipocytes, cardiac myocytes, smooth muscle, the liver, and pancreas. Curcumin's physicochemical properties and pharmacokinetics are closely connected with its therapeutic advantages in MetS and its components due to its high gastrointestinal absorption, drug-likeness, water solubility, and lipophilic nature. Curcumin is a CYP1A9 and CYP3A4 inhibitor. Although curcumin has a low bioavailability, it can be synthesized and administered to increase its pharmacokinetic features.. Curcumin needs to undergo therapeutic optimization and further study into its pharmacological structure before it can be used to treat MetS and its components.

Topics: Curcumin; Diabetes Mellitus, Type 2; Humans; Hypertension; Metabolic Syndrome; MicroRNAs; Obesity; PPAR gamma; Transcription Factors

Maintaining healthy body weight is an important component of any effective diabetes management plan. However, glycemic management using insulin generally leads to weight gain. In addition, weight loss medications prescribed for diabetes management are often associated with adverse side effects, which limit their long-term usage. Alternatively, nutrition intervention provides a safe, readily accessible, and inexpensive option for diabetes management. This study describes a composition of phytonutrients comprising berberine, cinnamaldehyde, and curcumin for glycemic and weight management. Functional complementarity between berberine, cinnamaldehyde, and curcumin provides an effective means to improve insulin sensitivity without increasing adiposity. In primary human omental preadipocytes, cinnamaldehyde and curcumin additively enhance insulin-stimulated activation of Akt2 and glucose uptake, whereas berberine inhibits de novo fatty acid biosynthesis and fat cell differentiation. In a diet-induced obesity murine model, a dietary supplement with berberine, cinnamaldehyde, and curcumin prevents weight gain, improves glucose tolerance, and reduces HbA1c, blood lipids, visceral adiposity, and liver steatosis. Collectively, the composition of phytonutrients comprising berberine, cinnamaldehyde, and curcumin protects against obesity and pre-diabetic conditions in a diet-induced obesity murine model. Safety and efficacy assessment of nutrition intervention using combined berberine, cinnamaldehyde, and curcumin for glycemic and weight management in future clinical trials are warranted.

Topics: Acrolein; Animals; Berberine; Blood Glucose; Curcumin; Diabetes Mellitus; Disease Models, Animal; Fatty Acids; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipids; Mice; Obesity; Phytochemicals; Weight Gain

Obesity is an established risk factor for metabolic disease. This study explores the functional complementation of anti-adipogenic phytonutrients for obesity prevention and management. Nine phytonutrients were selected based on their ability to affect the expression of one or more selected adipogenic biomarker proteins. The phytonutrients include berberine, luteolin, resveratrol, fisetin, quercetin, fucoidan, epigallocatechin gallate, hesperidin, and curcumin. The selected adipogenic biomarker proteins include PPARɣ, SREBP1c, FASN, PLIN1, FABP4, and β-catenin. Individually, phytonutrients had variable effects on the expression level of selected adipogenic biomarker proteins. Collectively, the functional complementation of nine phytonutrients suppressed de novo fatty acid biosynthesis via the negative regulation of PPARɣ, FASN, PLIN1, and FABP4 expression; activated glycolysis via the positive regulation of SREBP1c expression; and preserved cell-cell adhesion via the inhibition of β-catenin degradation. In primary human subcutaneous preadipocytes, the composition of nine phytonutrients had more potent and longer lasting anti-adipogenic effects compared to individual phytonutrients. In a diet-induced obesity murine model, the composition of nine phytonutrients improved glucose tolerance and reduced weight gain, liver steatosis, visceral adiposity, circulating triglycerides, low-density lipoprotein cholesterol, and inflammatory cytokines and chemokines. The functional complementation of anti-adipogenic phytonutrients provides an effective approach toward engineering novel therapeutics for the prevention and management of obesity and metabolic syndrome.

Topics: Adipocytes; Adipogenesis; Animals; Berberine; beta Catenin; Cholesterol; Curcumin; Cytokines; Fatty Acids; Glucose; Hesperidin; Humans; Lipoproteins, LDL; Luteolin; Mice; Obesity; Phytochemicals; PPAR gamma; Quercetin; Resveratrol; Sterol Regulatory Element Binding Protein 1; Triglycerides

Topics: Animals; Curcuma; Diet, High-Fat; Endoribonucleases; gamma-Aminobutyric Acid; Mice; Mice, Inbred C57BL; Mice, Obese; NADPH Oxidase 4; Obesity; Plant Extracts; Protein Serine-Threonine Kinases; Reactive Oxygen Species; Sirtuin 1

This study aims to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating induced inflammation and impaired brain neurotransmitters commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into four experimental groups. Group I, control, obese, fed on a high-fat diet (HFD), and Group II-IV, fed on HFD then given mangosteen extract (400 mg/kg/day) and/or Curcuma (80 mg/kg/day), or a mixture of both for 6 weeks. Plasma pro-inflammatory cytokines, leptin, and brain serotonin, dopamine, and glutamate were measured in the five studied groups. G. mangostana and Curcuma longa extracts demonstrate antioxidant and DPPH radical scavenging activities. Both induced a significant reduction in the weight gained, concomitant with a non-significant decrease in the BMI (from 0.86 to 0.81 g/cm2). Curcuma either alone or in combination with MPE was more effective. Both extracts demonstrated anti-inflammatory effects and induced a significant reduction in levels of both IL-6 and IL-12. The lowest leptin level was achieved in the synergistically treated group, compared to independent treatments. Brain dopamine was the most affected variable, with significantly lower levels recorded in the Curcuma and synergistically treated groups than in the control group. Glutamate and serotonin levels were not affected significantly. The present study demonstrated that mangosteen pericarp extract (MPE) and Curcuma were independently and in combination effective in treating obesity-induced inflammation and demonstrating neuroprotective properties.

Topics: Animals; Brain; Curcuma; Diet, High-Fat; Dopamine; Garcinia mangostana; Glutamates; Inflammation; Leptin; Male; Neurotransmitter Agents; Obesity; Plant Extracts; Rats; Rats, Wistar; Serotonin

Obesity prevalence continues to increase and contribute to metabolic diseases, potentially by driving systemic inflammation. Curcumin is an anti-inflammatory spice with claimed health benefits. However, mechanisms by which curcumin may reduce obesity-associated inflammation are poorly understood; thus, it is hypothesized that benefits of curcumin consumption may occur through reduced white adipose tissue (WAT) inflammation and/or beneficial changes in gut bacteria.. Male B6 mice are fed high-fat diets (HFD, 45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for 14 weeks. Curcumin supplementation significantly reduces adiposity and total macrophage infiltration in WAT, compared to HFD group, consistent with reduced mRNA levels of M1 (Cd80, Cd38, Cd11c) and M2 (Arginase-1) macrophage markers. Moreover, curcumin supplementation reduces expression of other key pro-inflammatory genes, such as NF-κB p65 subunit (p65), Stat1, Tlr4, and Il6, in WAT (p < 0.05). Using microbial 16S RNA sequencing, it is demonstrated that the relative abundance of the Lactococcus, Parasutterella, and Turicibacter genera are increased in the HFC group versus HFD.. Curcumin exerts protective metabolic effects in dietary obesity, in part through downregulation of adipose tissue inflammation, which may be mediated by alterations in composition of gut microbiota, and metabolism of curcumin into curcumin-O-glucuronide.

Topics: Adipose Tissue; Adipose Tissue, White; Animals; Curcumin; Diet, High-Fat; Gastrointestinal Microbiome; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity

Obesity increases the colorectal cancer risk, in part by elevating colonic proinflammatory cytokines. Curcumin (CUR) and supplemental vitamin B-6 each suppress colonic inflammation.. We examined whether the combination of CUR and vitamin B-6 amplifies each supplement's effects and thereby suppress obesity-promoted tumorigenesis.. Male Friend Virus B (FVB) mice (4-week-old; n = 110) received 6 weekly injections of azoxymethane beginning 1 week after arrival. Thereafter, they were randomized to receive a low-fat diet (10% energy from fat), a high-fat diet (HFD; 60% energy from fat), a HFD containing 0.2% CUR, a HFD containing supplemental vitamin B-6 (24 mg pyridoxine HCl/kg), or a HFD containing both CUR and supplemental vitamin B-6 (C + B) for 15 weeks. Colonic inflammation, assessed by fecal calprotectin, and tumor metrics were the primary endpoints. The anti-inflammatory efficacy of the combination was also determined in human colonic organoids.. HFD-induced obesity produced a 2.6-fold increase in plasma IL-6 (P < 0.02), a 1.9-fold increase in fecal calprotectin (P < 0.05), and a 2.2-fold increase in tumor multiplicity (P < 0.05). Compared to the HFD group, the C + B combination, but not the individual agents, decreased fecal calprotectin (66%; P < 0.01) and reduced tumor multiplicity and the total tumor burden by 60%-80% (P < 0.03) in an additive fashion. The combination of C + B also significantly downregulated colonic phosphatidylinositol-4,5-bisphosphate 3-kinase, Wnt, and NF-κB signaling by 31%-47% (P < 0.05), effects largely absent with the single agents. Observations that may explain how the 2 agents work additively include a 2.8-fold increased colonic concentration of 3-hydroxyanthranillic acid (P < 0.05) and a 1.3-fold higher colonic concentration of the active coenzymatic form of vitamin B-6 (P < 0.05). In human colonic organoids, micromolar concentrations of CUR, vitamin B-6, and their combination suppressed secreted proinflammatory cytokines by 41%-93% (P < 0.03), demonstrating relevance to humans.. In this mouse model, C + B is superior to either agent alone in preventing obesity-promoted colorectal carcinogenesis. Augmented suppression of procancerous signaling pathways may be the means by which this augmentation occurs.

Topics: Animals; Carcinogenesis; Colorectal Neoplasms; Curcumin; Diet, High-Fat; Dietary Supplements; Male; Mice; Mice, Inbred C57BL; Obesity; Pyridoxine; Vitamin B 6; Vitamins

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway's molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO

Topics: Animals; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Liver; Male; Metformin; Nanoparticles; Obesity; Oxidative Stress; Rats; Streptozocin; Zinc Oxide

Obesity has been recognized as a major risk factor for the development of chronic kidney disease, which is accompanied by increased renal inflammation, fibrosis, and apoptosis. C66 is a curcumin derivative that exerts anti-inflammatory effects by inhibiting the JNK pathway and prevents diabetic nephropathy. The present study investigates the possible protective effect of C66 on high-fat diet (HFD)-induced obesity-related glomerulopathy. Mice were fed with HFD for 8 weeks while some were treated with C66 every 2 days for 11 weeks. The HFD-fed mice developed renal dysfunction, as well as elevated triglyceride and cholesterol. Kidneys of the HFD-fed mice showed marked glomerular injuries, apoptosis, and inflammation with markedly increased cytokine production. Interestingly, treating HFD-fed mice with C66 remarkably reversed these pathological changes via inhibiting inflammation and NF-κB/JNK activation. In cultured mesangial cells, Palmitic Acid was able to activate the pro-fibrotic mechanisms, apoptosis, inflammatory response, and NF-κB and JNK signaling pathways, all of which could be attenuated by C66 treatment. In all, we demonstrated that curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation and apoptosis via targeting NF-κB and JNK. Our data suggest that C66 can be potentially used to prevent obesity-associated renal diseases warranting future investigations.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cholesterol; Chronic Disease; Curcumin; Cytokines; Diet, High-Fat; Kidney Diseases; Kidney Glomerulus; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; NF-kappa B; Obesity; Triglycerides

Obesity has become a major health problem that has rapidly prevailed over the past several decades worldwide. Curcumin, a natural polyphenolic compound present in turmeric, has been shown to have a protective effect on against obesity and metabolic diseases. However, its underlying mechanism remains largely unknown. Here, we show that the administration of curcumin significantly prevents HFD-induced obesity and decreases the fat mass of the subcutaneous inguinal WAT (iWAT) and visceral epididymal WAT (eWAT) in mice. Mechanistically, curcumin inhibits adipogenesis by reducing the expression of AlkB homolog 5 (ALKHB5), an m

Topics: 3T3-L1 Cells; Adipogenesis; Animals; Curcumin; Diet, High-Fat; Mice; Mice, Inbred C57BL; Obesity; TNF Receptor-Associated Factor 4; Ubiquitination

Curcumin (Cur) is a natural polyphenol with beneficial effect against obesity and related metabolic disorders, but its precise mechanisms of action remain to be defined due to its limited systemic bioavailability. We hypothesized that gut microbiota may be a prospective therapeutic target for Cur-induced metabolic benefits. This study aimed to investigate whether the metabolic adaptations resulting from Cur supplementation were mediated by the gut microbiota in high-fat diet (HFD)-fed obese mice. C57BL/6 mice were fed a control diet or a HFD diet with or without 0.2% Cur for 10 weeks. Lipid profiles, insulin sensitivity, hepatic metabolism, gut microbiota composition and short-chain fatty acid (SCFA) production were determined. Dietary Cur reduced fat mass, hepatic steatosis and circulating lipopolysaccharide levels and improved the insulin sensitivity in HFD-fed mice. More importantly, Cur supplementation modulated the gut microbiota composition and ameliorated intestinal dysbiosis by decreasing the ratio of Firmicutes/Bacteroidetes and endotoxin-producing Desulfovibrio bacteria and increasing the abundance of Akkermansia population and SCFA-producing bacteria, such as Bacteroides, Parabacteroides, Alistipes and Alloprevotella, along with increases in caecal and colonic SCFA concentrations. These dominant bacterial genera altered by Cur showed strong correlations with the obesity-related metabolic parameters in HFD-fed mice. In conclusion, our data suggest that Cur alleviated metabolic features of hepatic steatosis and insulin resistance in HFD-fed obese mice, which might be associated with the modulation of gut microbiota composition and metabolites.

Topics: Animals; Curcumin; Diet, High-Fat; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Obesity; Prospective Studies

Topics: Animals; Anti-Obesity Agents; Bile Acids and Salts; Curcumin; Diet, High-Fat; Energy Metabolism; G-Protein-Coupled Receptor Kinase 5; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Thermogenesis; Uncoupling Protein 1; Weight Gain

Obese patients are often accompanied by hyperleptinemia and prone to develop liver fibrosis. Accumulating data including those obtained from human studies suggested the promotion role of leptin in liver fibrosis. The remodeling of the DNA methylation is an epigenetic mechanism for regulating gene expression and is essential for hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Leptin increases the expression of methionine adenosyltransferase 2A (MAT2A) which is associated with DNA methylation and HSC activation. Curcumin, an active polyphenol of the golden spice turmeric, inhibits leptin-induced HSC activation and liver fibrogenesis. Thus, the present research aimed to investigate the influence of curcumin on the roles of leptin in MAT2A expression in HSCs.. The in vivo experiments were conducted by using leptin-deficient obese mice. The gene expressions were examined by Western blot, real-time PCR, promoter activity assay, and immunostaining analysis.. Curcumin reduced leptin-induced MAT2A expression. JNK signaling contributed to leptin-induced increase in MAT2A level, which could be interrupted by curcumin treatment. Curcumin inhibited leptin-induced MAT2A promoter activity by influencing MAT2A promoter fragments between -2,847 bp and - 2,752 bp and between -2,752 bp and +49 bp. The effect of curcumin on leptin-induced MAT2A expression paralleled the reductions in leptin-induced activated HSCs and liver fibrosis.. These results might have implications for curcumin inhibition of the liver fibrogenesis in obese patients with hyperleptinemia.

Topics: Animals; Curcumin; Hepatic Stellate Cells; Leptin; Liver Cirrhosis; Male; MAP Kinase Signaling System; Methionine Adenosyltransferase; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity

Obesity can induce chronic low-grade inflammation via oxidative stress. Tetrahydrocurcumin (THC) is a major curcumin metabolite with anti-inflammatory and antioxidant effects, but little is known about its effects on the skin of obese individuals. Thus, the aim of this study was to investigate the effects of THC on inflammatory cytokine production, oxidative stress, and autophagy in the skin of mice with high-fat diet- (HFD-) induced obesity. Eight-week-old C57BL/6J mice were fed a regular diet, HFD (60% of total calories from fat), or HFD supplemented with THC (100 mg/kg/day orally) for 12 weeks. We measured their body weights during the experimental period. After 12-week treatments, we performed western blotting and real-time polymerase chain reaction analyses on skin samples to evaluate the expression of inflammatory cytokines, oxidative stress markers, and autophagy markers. We observed higher tumor necrosis factor-

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Autophagy; Body Weight; Curcumin; Cytokines; Diet, High-Fat; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oxidative Stress; Signal Transduction; Skin; Skin Diseases; Temperature

The prevalence of overweight and obesity and associated comorbidities has progressively risen. Curcumin, the active ingredient in turmeric, and turmeric aqueous extract, a concentrated form, have been reported to have beneficial effects in treatment of cardiovascular diseases and their risk factors. However, turmeric has not been studied in its natural form.. The present study planned to evaluate the beneficial effects of turmeric in its natural form on obesity-related, cardiovascular-disease risk factors in overweight or obese females.. The study used a pre-post, single-arm design.. The study took place in the Department of Physiology at Imam Abdulrahman Bin Faisal University (Dammam, Saudi Arabia).. The participants were 36 young female students at the university, with a body mass index ≥ 23 kg/m2.. Participants received a daily dose of 2 g/d of turmeric in capsules for 90 d.. Anthropometric measures, blood pressure, serum homocysteine, and mental health status- stress, anxiety, depression scores-were recorded at baseline and postintervention. Dietary intake and physical activity (confounding variables) were also measured.. The following anthropometric measures were reduced significantly between baseline and postintervention: (1) body weight-73.47 vs 72.45 kg (P = .04), (2) body mass index-28.75 vs 28.27 kg/m2 (P = .02), (3) waist circumference-81.85 vs 77.96 cm (P = .01), (4) hip circumference-102.72 vs 98.10 cm (P = .001), (5) body fat %-34.34 vs 32.58 (P = .00), (6) systolic blood pressure-119.12 vs 115.92 mm Hg (P = .04), and (7) anxiety scores-7.88 vs 4.73 (P = .03), as compared by paired t test. Homocysteine levels and stress and depression scores showed no significant changes. Dietary intake and physical activity did not vary significantly throughout the study period.. Turmeric has the ability to reduce weight, decrease body fat percentage, lower systolic blood pressure, and relieve anxiety for young, obese and overweight females, when given at 2 g/d for 90 d.

Topics: Body Mass Index; Cardiovascular Diseases; Curcuma; Female; Heart Disease Risk Factors; Homocysteine; Humans; Mental Health; Obesity; Overweight; Plant Extracts; Risk Factors

Dietary polyphenols in plant extracts are being widely investigated due to their great health-promoting activities and effect on modulating gut ecology. In turn, gut microbiota, plays a vital role in the biological activities of phenolic metabolites, particularly after the intake of food rich in polyphenols, such as plant extracts. However, this two-way relationship between polyphenols and microbiota is poorly understood. We prepared curcuma and mangosteen methanol extracts and fed them to healthy, lean, and obese rats over a period of 10 weeks. Subsequent alterations in the gut microbiota were determined. Overall, Firmicutes were more abundant than Bacteroidetes throughout the experiment. A particular increase of gram-positive cocci species and a significant decrease in both Clostridium and Bacteroides species were noted primarily in the first weeks of both plant extract intake in the control and lean rats. Compared to obese rats fed a regular diet, obese rats fed plant extracts showed an increase in Enterobacteriacea, Clostridium, and Bacteroides species and a decrease in gram-positive cocci in the first weeks of treatment with the last weeks of treatment the results at the species level were inverted.

Topics: Animals; Curcuma; Garcinia mangostana; Gastrointestinal Microbiome; Obesity; Plant Extracts; Rats

Sargassum fusiforme, a nutritious edible brown alga, has been widely suggested to play an important role in the development of functional food because of its multiple biological activities. The aim of this study was to explore the anti-obesity effect of the combination of Sargassum fusiforme with extracts of fruit and vegetable by comparing the effects of Sargassum fusiforme (S), Sargassum fusiforme together with pomegranate peel extract (SP), Sargassum fusiforme together with turmeric extract (ST) and Sargassum fusiforme together with turmeric extract and pomegranate peel extract (C) on diet-induced obese C57BL/6J mice. Long-term consumption of a high-fat diet can lead to high levels of blood lipid, increase adipocyte size, and cause lipid metabolism dysfunction and gut microbiota dysbiosis. According to the results of the experiments, SP and ST were more effective in reducing lipid levels and fat accumulation than S; and, C exhibited the strongest efficacy compared with the other three supplements. ST and C also regulated adipocytokines and had significant effects on the gene expression of lipid metabolism. We also found that C alleviated the imbalance of intestinal flora caused by a high-fat diet to a certain extent. In conclusion, SP, ST and C have anti-obesity potentials, which can be used as alternative ingredients in the formula of functional food for obese people.

Topics: Adipose Tissue; Animals; Curcuma; Diet, High-Fat; Dietary Supplements; Enzyme Inhibitors; Fruit; Gastrointestinal Microbiome; Glucose; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Pancreas; Plant Extracts; Pomegranate; Sargassum

Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat storage in the liver and it is strongly linked with metabolic syndrome including obesity, insulin resistance, dyslipidemia and hypertension. Curcumin5-8 (CUR5-8) is a synthetic derivative of naturally active curcumin (CUR) that has anti-oxidative and anti-inflammatory properties. In the present study, we investigated the effects of CUR5-8, a novel CUR analog, on hepatic steatosis in mice with high-fat diet (HFD)-induced obesity.. Based on their diets for 13 weeks, the mice were categorized into the following six groups: regular diet (RD, n = 10), RD with CUR (RD + CUR, 100 mg/kg/day, n = 10), RD with CUR5-8 (RD + CUR5-8, 100 mg/kg/day, n = 10), high-fat diet-induced obese mice (HFD, n = 10), HFD with CUR (HFD + CUR, 100 mg/kg/day, n = 10), and HFD with CUR5-8 (HFD + CUR5-8, 100 mg/kg/day, n = 10) for 13 weeks. Hematoxylin and eosin (H&E) staining of the sections revealed hepatic steatosis.. CUR5-8 administration prevented increase in body and liver weights in mice with HFD-induced obesity. Compared to the HFD group, insulin resistance was significantly improved in the HFD + CUR5-8 group. Serum alanine aminotransferase level, which is an indicator of liver damage, was also decreased after CUR5-8 administration. H&E staining revealed that CUR5-8 treatment decreased hepatic steatosis in mice with HFD-induced obesity. Interestingly, CUR5-8, and not CUR, decreased the elevated liver triglyceride level induced by the HFD.. These findings suggest that CUR5-8 ameliorates insulin resistance and hepatic steatosis in mice with HFD-induced obesity.

Topics: Animals; Autophagy; Cells, Cultured; Curcumin; Cytoprotection; Diet, High-Fat; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Weight Gain

The development of obesity-associated complications is related to various pathogenic events including chronic inflammation, oxidative stress and generation of advanced glycation end products (AGEs). Due to their antioxidant, anti-inflammatory and antiglycation properties, trigonelline and curcumin are interesting candidates to counteract complications of obesity and diabetes mellitus. The current study aimed to investigate the effects of treatment with curcumin or trigonelline mixed into yoghurt, alone or in combination, on mice fed high-fat diet (HFD); the focus was mainly on the potential of these phytochemicals to counteract oxidative and glycative stress. Yoghurt alone improved glucose tolerance and reduced proinflammatory cytokine levels in HFD mice; however, it did not affect the antioxidant status. Trigonelline-enriched yoghurt prevented fat accumulation in adipose tissue, improved both insulin sensitivity and glucose tolerance and exerted anti-inflammatory and antiglycation activities (reduced AGEs and AGE receptor levels and increased the levels of components related to AGE detoxification) in liver and kidney of HFD mice. Curcumin-enriched yoghurt exerted anti-inflammatory and potent antioxidant properties (increased antioxidant enzyme activities and decreased lipid peroxidation) in liver and kidney of HFD mice. However, several beneficial effects were nullified when trigonelline and curcumin were administered in combination. Trigonelline and curcumin have emerged as promising complementary therapy candidates for liver and kidney complications associated with obesity. However, the administration of these phytochemicals in combination, at least in HFD mice, was not effective; inhibition of biotransformation processes and/or the reaching of toxic doses during combined treatment may be prevailing over the individual pharmacodynamic actions of these phytochemicals.

Topics: Alkaloids; Animals; Antioxidants; Biomarkers; Blood Glucose; Body Weight; Curcumin; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Glucose; Glucose Tolerance Test; Glycosylation; Homeostasis; Inflammation; Kidney; Lipid Peroxidation; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Oxidative Stress

Worldwide rates of Western-diet-induced obesity epidemics are growing dramatically. Being linked with numerous comorbidities and complications, including cardiovascular disease, type 2 diabetes, cancer, chronic inflammation, and osteoarthritis (OA), obesity represents one of the most threatening challenges for modern healthcare. Mouse models are an invaluable tool for investigating the effects of diets and their bioactive components against high fat diet (HFD)-induced obesity and its comorbidities. During recent years, very high fat diets (VHFDs), providing 58-60% kcal fat, have become a popular alternative to more traditional HFDs, providing 40-45% total kcal fat, due to the faster induction of obesity and stronger metabolic responses. This project aims to investigate if the 60% fat VHFD is suitable to evaluate the protective effects of curcumin in diet-induced obesity and osteoarthritis. B6 male mice, prone to diet-induced metabolic dysfunction, were supplemented with VHFD without or with curcumin for 13 weeks. Under these experimental conditions, feeding mice a VHFD for 13 weeks did not result in expected robust manifestations of the targeted pathophysiologic conditions. Supplementing the diet with curcumin, in turn, protected the animals against obesity without significant changes in white adipocyte size, glucose clearance, and knee cartilage integrity. Additional research is needed to optimize diet composition, curcumin dosage, and duration of dietary interventions to establish the VHFD-induced obesity for evaluating the effects of curcumin on metabolic dysfunctions related to obesity and osteoarthritis.

Topics: Adipocytes; Animals; Curcumin; Diet, High-Fat; Dietary Fats; Disease Models, Animal; Humans; Mice; Obesity; Osteoarthritis

The circadian rhythm of biological systems is an important consideration in developing health interventions. The immune and oxidative defense systems exhibit circadian periodicity, with an anticipatory increase in activity coincident with the onset of the active period. Spice consumption is associated with enhanced oxidative defense. The objective of this study was to test the feasibility of a protocol, comparing the effects of morning vs. evening consumption of turmeric on urine markers of oxidative stress in obese, middle-aged adults. Using a within-sample design, participants received each of four clock time x treatment administrations, each separated by one week: morning turmeric; evening turmeric; morning control; evening control. Participants prepared for each lab visit by consuming a low-antioxidant diet for two days and fasting for 12 h. Urine was collected in the lab at baseline and one-hour post-meal and at home for the following five hours. The results showed that the processes were successful in executing the protocol and collecting the measurements and that participants understood and adhered to the instructions. The findings also revealed that the spice treatment did not elicit the expected antioxidant effect and that the six-hour post-treatment urine collection period did not detect differences in urine endpoints across treatments. This feasibility study revealed that modifications to the spice treatment and urine sampling timeline are needed before implementing a larger study.

Topics: Adult; Biomarkers; Circadian Rhythm; Curcuma; Feasibility Studies; Humans; Middle Aged; Obesity; Oxidative Stress

LI85008F is a proprietary combination of leaf extracts of Moringa oleifera, Murraya koeingii, and extract of Curcuma longa rhizome. This herbal extract combination is an effective weight loss supplement for overweight and obese subjects. The present study aimed to investigate the thermogenic potential of the LI85008F in high-fat diet (HFD)-induced obese Sprague Dawley rats.. Seven rats received a regular diet (RD), and twenty-one rats received a high-fat diet (HFD) for 56 days. On day 28, the HFD-fed rats were randomized into three groups (n = 7). Starting from day 29 through day 56, one HFD-fed group received daily oral gavage of 0.5% Carboxymethylcellulose Sodium (CMC) alone (HFD), and the remaining two groups received 100 and 250 mg/kg LI85008F (LI85008F-100 and LI85008F-250, respectively). Body weight, fat mass, fat cell size, liver weight, liver triglyceride were measured. The energy metabolism parameters were measured using indirect calorimetry. In serum, the metabolic and endocrine markers were analyzed. The adipogenic and thermoregulatory proteins expression in the white adipose tissue (WAT) were analyzed using an immunoblot assay.. Supplementation with both doses of LI85008F significantly increased resting energy expenditure (REE) in the obese rats. The LI85008F-250 rats showed significant up-regulation of uncoupling protein-1 (UCP-1) expression, as compared with the HFD rats. LI85008F significantly reduced body weight gain, fat mass, fat cell size, liver weight, and hepatic triglycerides. Serum triglyceride, total cholesterol, glucose, leptin, and fat cell markers were significantly reduced in LI85008F-supplemented rats compared to the HFD rats.. The present data suggest that LI85008F reduces body fat mass and controls body weight gain via increasing energy metabolism in combination with reduced lipogenesis in diet-fed obese rats.

Topics: Animals; Blotting, Western; Calorimetry, Indirect; Curcuma; Diet, High-Fat; Energy Metabolism; Male; Moringa oleifera; Murraya; Obesity; Plant Extracts; Plant Leaves; Plant Preparations; Rats; Rats, Sprague-Dawley

High-fat diets (HFDs) and adiposity increase colorectal cancer risk, in part by elevating pro-inflammatory cytokines that activate pro-cancerous signaling pathways. Curcumin (CUR), a dietary polyphenol and salsalate (SAL), an non-steroidal anti-inflammatory drug (NSAID) lacking the gastrotoxicity of aspirin, each suppress inflammatory signaling, but via different cellular pathways.. A/J mice (n = 110) are fed a low-fat diet (LFD, 10% kcal), a HFD (60% kcal), a HFD containing 0.4% CUR, a HFD containing 0.3% SAL, or a HFD containing both agents (CUR/SAL). All mice receive six injections of azoxymethane. Compared to LFD-fed mice, HFD-fed mice display elevated colonic cytokines, crypt cell proliferation, and increased tumorigenesis (p < 0.05). CUR/SAL significantly reduces colonic cytokines (p < 0.01), suppresses activation of the PI3K/Akt/mTOR/NF-κB/Wnt pathways (p < 0.01), activates AMPK (p < 0.01), attenuates abnormal proliferation of the colonic mucosa (p < 0.05), and reduces tumor multiplicity and burden (p < 0.05), in comparison to the HFD control. In contrast, CUR or SAL alone does not suppress abnormal crypt cell proliferation or tumor multiplicity, and is largely ineffective in modifying activation of these signaling pathways.. These observations demonstrate the superiority of the CUR/SAL over the individual agents and provide a scientific basis for future translational studies in obese subjects and/or those habitually consuming HFDs.

Topics: Adiposity; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Proliferation; Colitis; Colorectal Neoplasms; Curcumin; Diet, High-Fat; Intestinal Mucosa; Male; Mice, Inbred Strains; Obesity; Precancerous Conditions; Salicylates; Signal Transduction

Turmeric is a well-known functional food exhibiting multiple biological activities in health and disease. However, low aqueous solubility and poor bioavailability limit its therapeutic potential. Herein, we investigated the utility of nanoemulsions as a carrier to improve the efficacy of turmeric. Compared with turmeric extract (TE), 5% TE-loaded nanoemulsion (TE-NE), which contains 20-fold lower curcumin content than TE, achieved similar inhibition of palmitate-induced lipotoxicity in HepG2 cells. Exposure of HepG2 cells to 5% TE-NE also suppressed the palmitate-induced accumulation of lipid vacuoles and reactive oxygen species comparably with TE, and was accompanied by decreased levels of sterol regulatory element-binding protein (SREBP)-1, peroxisome proliferator-activated receptor-γ2 (PPAR-γ2), cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP). Consistent with these effects in HepG2 cells, oral administration of 5% TE-NE to mice fed a high fat diet (HFD) markedly suppressed lipid accumulation in liver, leading to a significant reduction in body weight and adipose tissue weight, equivalent to the effects observed with TE. Compared with TE, 5% TE-NE also equivalently inhibited the levels of SREBP-1, PPAR-γ2, cleaved caspase-3, and PARP in the liver of mice fed a HFD. Furthermore, TE and 5% TE-NE significantly improved serum lipid profiles in a similar manner. These observations indicate that nanoemulsions can improve the efficacy of turmeric, thereby eliciting more potent biological efficacy against palmitate- and high fat diet (HFD)-induced cellular damage.

Topics: Animals; Body Weight; Cell Survival; Curcuma; Diet, High-Fat; Dose-Response Relationship, Drug; Drug Carriers; Emulsions; Hep G2 Cells; Humans; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Obesity; Palmitates; Plant Extracts; Treatment Outcome

Vascular endothelial dysfunction is a potential risk factor for cardiovascular disease. This study evaluated the effect of curcumin on factors associated with vascular dysfunction using rats fed a high-sucrose, high-fat (HSF) diet. The experiment included 2 animal feeding phases. In the first feeding phase, male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 8) was fed a standard diet (AIN-93G) and the HSF group (n = 24) was fed an HSF diet for 8 weeks to induce obesity. In the second feeding phase, lasting 4 weeks, the HSF group was randomly divided into 3 subgroups: the O group (n = 8) continued feeding on the HSF diet, the OA group (n = 8) had the HSF diet replaced with AIN-93G, and the OC group (n = 8) was fed the HSF diet supplemented with curcumin (300 mg/kg body weight daily). After 8 weeks, the HSF diet significantly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), insulin, homeostatic model assessment insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) but significantly reduced levels of nitric oxide (NO) and high-density lipoprotein cholesterol (HDL-C). After dietary intervention, the OA and OC groups exhibited significantly lower levels of AST, ALT, HOMA-IR, cholesterol, LDL-C, Hcy, CRP, VCAM-1, and ICAM-1 and higher levels of NO and catalase (CAT) activity compared with the O group. Superoxide dismutase, CAT, and glutathione peroxidase activities were increased in the OA group, while CAT levels were enhanced in the OC group. In conclusion, this study showed that curcumin supplementation and diet modification can inhibit HSF diet-induced vascular dysfunction potentially by enhancing NO production and antioxidant enzyme activities, thereby suppressing inflammation and oxidative damage in the vascular endothelium.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Biomarkers; C-Reactive Protein; Cholesterol; Curcumin; Diet, High-Fat; Dietary Sucrose; Endothelium, Vascular; Homocysteine; Inflammation; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Liver; Male; Malondialdehyde; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Risk Factors; Vascular Cell Adhesion Molecule-1; Vascular Diseases

White adipose tissue (eWAT) plays a crucial role in preventing metabolic syndrome. We aimed to investigate WAT distribution and gene expression and lipidomic profiles in epididymal WAT (eWAT) in diet-induced obese mice, reflecting a Western-style diet of humans to elucidate the bioactive properties of the dietary antioxidant curcumin in preventing lifestyle-related diseases. For 16 weeks, we fed C57BL/6J mice with a control diet, a high-fat, high-sucrose and high-cholesterol Western diet or Western diet supplemented with 0.1% (w/w) curcumin. Although the dietary intake of curcumin did not affect eWAT weight or plasma lipid levels, it reduced lipid peroxidation markers' levels in eWAT. Curcumin accumulated in eWAT and changed gene expressions related to eukaryotic translation initiation factor 2 (eIF2) signalling. Curcumin suppressed eIF2α phosphorylation, which is induced by endoplasmic reticulum (ER) stress, macrophage accumulation and nuclear factor-κB (NF-κB) p65 and leptin expression, whereas it's anti-inflammatory effect was inadequate to decrease TNF-α and IFN-γ levels. Lipidomic and gene expression analysis revealed that curcumin decreased some diacylglycerols (DAGs) and DAG-derived glycerophospholipids levels by suppressing the glycerol-3-phosphate acyltransferase 1 and adipose triglyceride lipase expression, which are associated with lipogenesis and lipolysis, respectively. Presumably, these intertwined effects contribute to metabolic syndrome prevention by dietary modification.

Topics: Adipose Tissue, White; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diet, High-Fat; Eukaryotic Initiation Factor-2; Gene Expression; Gene Expression Profiling; Humans; Lipid Metabolism; Male; Mice, Inbred C57BL; Obesity; Signal Transduction

Obesity as a dominant problem in developed countries which is known to be basic step of so many diseases is subjected to find a solution for in this work. Curcumin containing polyvinyl alcohol-gelatin nanofibers which ranging from 200 to 250 nm in diameter as a transdermal drug delivery system for declining volume of subcutaneous adipose tissue is investigated here. Morphology and synthesis method of nanofibers is designed and optimized by statistical software and a totally uniform and reproducible method of synthesis is used for preparation of a transdermal patch. Effectiveness of delivery system in transport of drug through skin is confirmed by side by side arrangement transdermal diffusion cells. This transdermal patch used for animal test showed 4 to 7% decrease in total amount of adipose tissue estimated by whole body magnetic resonance imaging technique.

Topics: Adipose Tissue; Administration, Cutaneous; Animals; Cholesterol; Curcumin; Diet, High-Fat; Drug Liberation; Gelatin; Leptin; Magnetic Resonance Imaging; Nanofibers; Obesity; Polyvinyl Alcohol; Rats; Transdermal Patch; Triglycerides

Diet-induced obesity is strongly associated with nonalcoholic fatty-liver disease (NAFLD) and insulin resistance. We aimed to investigate the in vivo therapeutic value of tetrahydrocurcumin (THC) intervention in high-fat-diet (HFD)-induced obesity and hepatic steatosis. C57BL/6 mice were fed an HFD for 10 weeks, and then they received 20 or 100 mg/kg THC along with the HFD for another 10 weeks. Mice fed an HFD for 20 weeks experienced obesity, hepatic steatosis, hyperlipidemia, and insulin resistance. Tetrahydrocurcumin (THC) intervention for 10 weeks significantly reduced adiposity (epididymal-fat weights of 6.6 ± 0.4 g for the HFD-only group and 5.3 ± 0.8 and 5.6 ± 0.7 g for the HFD with 20 mg/kg THC and HFD with 100 mg/kg THC groups, respectively; p < 0.05) via downregulation of adipogenic factors. Inflammatory macrophage infiltration and polarization were decreased by THC in mouse epididymal adipose tissues. In the liver, THC markedly alleviated steatosis by approximately 28-37% ( p < 0.05) via the downregulation of lipogenesis, the activation of AMP-activated protein kinase (AMPK), and the increase of fatty acid oxidation. Elevated blood glucose and insulin resistance were also improved by THC, which might be caused by regulation of the hepatic insulin signaling cascade, gene transcription involved in glucose metabolism, and reduced macrophage infiltration in the liver and adipose tissue. Our results demonstrated the beneficial effects of THC-mediated intervention against obesity and NAFLD as well as other metabolic syndromes, revealing a novel therapeutic use of THC in obese populations.

Topics: Adipose Tissue; Adiposity; Animals; Curcumin; Diet, High-Fat; Glucose; Humans; Insulin; Lipid Metabolism; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity

Studies have indicated that extraweight and obesity induce chronic inflammation, which can lead to other diseases such as cancers.. To evaluate the effects of two weight-lowering and anti-inflammatory agents including cinnamon, and turmeric, on serum levels of interleukin-17 (IL-17) as a pro-inflammatory cytokine.. In this study, 64 rats were designated in eight groups. The control group received normal diet. The other groups were fed with normal diet plus high cinnamon (3 mg/ml), high turmeric (3 mg/ml), high-fructose solution (30%), fructose solution with low (0.15 mg/ml) and high doses (3 mg/ml) of cinnamon and turmeric three times per week. The serum level of IL-17F was measured by enzyme-linked immunosorbent assay (ELISA).. High fructose consumption led to an increase in the weight and serum level of IL-17. While, feeding with cinnamon and turmeric caused to decline weight but, surprisingly increased IL-17F levels.. Although, some studies have showed that cinnamon and turmeric supplementation decreased IL-17F under the standard diet, in the presence of high fructose diet and extraweight their effects were reversed and caused an increase in serum level of IL-17F.

Topics: Animals; Anti-Inflammatory Agents; Cinnamomum zeylanicum; Curcuma; Diet; Disease Models, Animal; Drug Therapy, Combination; Fructose; Humans; Interleukin-17; Male; Obesity; Plant Extracts; Rats; Rats, Wistar

Topics: Animals; Body Weight; CD36 Antigens; Curcumin; Cyclic AMP Response Element-Binding Protein; Diet, High-Fat; Fatty Liver; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; PPAR gamma; Signal Transduction

Weight regain, adipose tissue growth, and insulin resistance can occur within days after the cessation of regular dieting and exercise. This phenomenon has been attributed, in part, to the actions of stress hormones as well as local and systemic inflammation. We investigated the effect of curcumin, a naturally occurring polyphenol known for its anti-inflammatory properties and inhibitory action on 11β-HSD1 activity, on preserving metabolic health and limiting adipose tissue growth following the cessation of daily exercise and caloric restriction (CR). Sprague-Dawley rats (6-7 wk old) underwent a "training" protocol of 24-h voluntary running wheel access and CR (15-20 g/day; ~50-65% of ad libitum intake) for 3 wk ("All Trained") or were sedentary and fed ad libitum ("Sed"). After 3 wk, All Trained were randomly divided into one group which was terminated immediately ("Trained"), and two detrained groups which had their wheels locked and were reintroduced to ad libitum feeding for 1 wk. The wheel locked groups received either a daily gavage of a placebo ("Detrained + Placebo") or curcumin (200 mg/kg) ("Detrained + Curcumin"). Cessation of daily CR and exercise caused an increase in body mass, as well as a 9- to 14-fold increase in epididymal, perirenal, and inguinal adipose tissue mass, all of which were attenuated by curcumin ( P < 0.05). Insulin area under the curve (AUC) during an oral glucose tolerance test, HOMA-IR, and C-reactive protein (CRP) were elevated 6-, 9-, and 2-fold, respectively, in the Detrained + Placebo group vs. the Trained group (all P < 0.05). Curcumin reduced insulin AUC, HOMA-IR, and CRP vs. the placebo group (all P < 0.05). Our results indicate that curcumin has a protective effect against weight regain and impaired metabolic control following a successful period of weight loss through diet and exercise, perhaps via inhibition of glucocorticoid action and inflammation. NEW & NOTEWORTHY Weight regain after dieting and exercise is a common phenomenon plaguing many individuals. The biological mechanisms underlying weight regain are incompletely understood and are likely multifactorial. In this paper, we examined the metabolic implications of curcumin, a compound known for its anti-inflammatory properties and inhibitory action on the enzyme 11β-HSD1, in a rodent model of adiposity rebound after the cessation of diet and exercise.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipose Tissue; Animals; Caloric Restriction; Corticosterone; Curcumin; Diet; Glucose Intolerance; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Muscle, Skeletal; Obesity; Physical Conditioning, Animal; Random Allocation; Rats; Rats, Sprague-Dawley; Weight Gain

We found previously that short-term curcumin gavage stimulated mouse hepatic fibroblast growth factor 21 (Fgf21) expression. Here we conducted mechanistic exploration and investigated the potential pathophysiological relevance on this regulation. Fgf21 stimulation was observed at messenger RNA and protein levels in mice with daily curcumin gavage for 4 or 8 days and in primary hepatocytes with curcumin treatment. Using peroxisome proliferator-activated receptor α (PPARα) agonist and antagonist, along with luciferase reporter and chromatin immune-precipitation approaches, we determined that curcumin stimulates Fgf21 transcription in a mechanism involving PPARα activation. High-fat diet (HFD) feeding also increased mouse hepatic and serum Fgf21 levels, whereas dietary curcumin intervention attenuated these increases. We found that HFD feeding reduced hepatic expression levels of genes that encode FGFR1 and βKlotho, PGC1α, and the targets of the PPARα-PGC1α axis, whereas concomitant curcumin intervention restored or partially restored their expression levels. Importantly, hepatocytes from HFD-fed mice showed a loss of response to FGF21 treatment on Erk phosphorylation and the expression of Egr1 and cFos; this response was restored in hepatocytes from HFD-fed mice with curcumin intervention. This investigation expanded our mechanistic understanding of the metabolic beneficial effects of dietary curcumin intervention involving the regulation of Fgf21 production and the attenuation of HFD-induced Fgf21 resistance.

Topics: Animals; Curcumin; Diet, High-Fat; Fibroblast Growth Factors; Gene Expression Regulation; Hep G2 Cells; Humans; Liver; Male; Metabolic Diseases; Mice; Obesity; PPAR alpha

Obesity is caused by excessive accumulation of body fat and is closely related to complex metabolic diseases. Adipogenesis is a key process that is required in adipocyte hypertrophy in the development of obesity. Curcumin (Cur) has been reported to inhibit adipocyte differentiation, but the inhibitory effects of other curcuminoids present in turmeric, such as demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), on adipogenesis have not been investigated. Here, we investigated the effects of curcuminoids on adipogenesis and the molecular mechanisms of adipocyte differentiation. Among three curcuminoids, BDMC was the most effective suppressor of lipid accumulation in adipocytes. BDMC suppressed adipogenesis in the early stage primarily through attenuation of mitotic clonal expansion (MCE). In BDMC-treated preadipocytes, cell cycle arrest at the G0/G1 phase was found after initiation of adipogenesis and was accompanied by downregulation of cyclin A, cyclin B, p21, and mitogen-activated protein kinase (MAPK) signaling. The protein levels of the adipogenic transcription factors peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding proteins (C/EBP)α were also reduced by BDMC treatment. Furthermore, 0.5% dietary BDMC (w/w) significantly lowered body weight gain and adipose tissue mass in high-fat diet (HFD)-fed mice. The results of H&E staining showed that dietary BDMC reduced hypertrophy in adipocytes. These results demonstrate for the first time that BDMC suppressed adipogenesis in 3T3-L1 adipocytes and prevented HFD-induced obesity. Our results suggest that BDMC has the potential to prevent obesity.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Curcumin; Diarylheptanoids; Diet, High-Fat; Down-Regulation; Humans; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Obesity; PPAR gamma

The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats.. Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment.. High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA-IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF-α and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition.. Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Curcumin; Diet, High-Fat; Dietary Supplements; Fasting; Inflammation; Inflammation Mediators; Insulin; Insulin Resistance; Liver; Male; Muscle, Skeletal; Obesity; Oxidative Stress; Rats; Rats, Wistar; Triglycerides

Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Lepr(db/db) on the Kaliss background).. In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity.. These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance.

Topics: 3T3-L1 Cells; Animals; Body Composition; Cell Survival; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Supplements; Glycated Hemoglobin; Homeostasis; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Mice; Mice, Inbred C57BL; Obesity; Oligopeptides; Pentacyclic Triterpenes; Polyphenols; Proteasome Inhibitors; Receptors, Leptin; Triterpenes

Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.

Topics: Adipose Tissue; Animals; Blood Glucose; Cholesterol; Curcumin; Diabetes Mellitus, Type 2; Diet, High-Fat; Down-Regulation; Energy Metabolism; Insulin Resistance; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Sterol Regulatory Element Binding Proteins; Triglycerides; Weight Gain

Indigestible carbohydrates may improve obesity. Spent turmeric contains high levels of dietary fibre and resistant starch (RS), which have fermentation potential in vitro. We hypothesised that indigestible carbohydrates in spent turmeric might prevent obesity development. In the first study, rats were administered 10% turmeric powder (TP) or spent turmeric powder (STP) in a high-fat (HF) diet for 28 d. In the second study, rats were fed 10% STP in a HF diet with or without antibiotics for 15 d. In the third study, rats were treated with a STP-containing suspension. In study 1, the TP and STP diet increased the caecal short-chain fatty acid (SCFA) content compared to that of a control diet. The lower energy intake in the TP and STP group was strongly related to the decrease in visceral fat weight. In study 2, after caecal fermentation suppression with antibiotics, STP treatment decreased the visceral fat mass. In study 3, the plasma glucose levels and incremental area under the curve (AUC) after ingestion of a STP-containing suspension were lower than those after ingestion of suspension alone. These findings suggest the reduction of carbohydrate absorption during the gastrointestinal passage after TP and STP treatment. Our data indicate that the reduced obesity development in rats fed a HF diet may be attributed to the low metabolisable energy density of carbohydrates in the spent turmeric, independent of SCFA-mediated factors.

Topics: Animals; Cecum; Curcuma; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats; Energy Intake; Fatty Acids, Volatile; Humans; Male; Obesity; Rats; Rats, Sprague-Dawley

Dehydrozingerone (DHZ) exerts beneficial effects on human health; however, its mechanism of action remains unclear. Here, we found that DHZ suppressed high-fat diet-induced weight gain, lipid accumulation and hyperglycaemia in C57BL/6 mice and increased AMP-activated protein kinase (AMPK) phosphorylation and stimulated glucose uptake in C2C12 skeletal muscle cells. DHZ activated p38 mitogen-activated protein kinase (MAPK) signalling in an AMPK-dependent manner. Inhibiting AMPK or p38 MAPK blocked DHZ-induced glucose uptake. DHZ increased GLUT4 (major transporter for glucose uptake) expression in skeletal muscle. Glucose clearance and insulin-induced glucose uptake increased in DHZ-fed animals, suggesting that DHZ increases systemic insulin sensitivity in vivo. Thus, the beneficial health effects of DHZ could possibly be explained by its ability to activate the AMPK pathway in skeletal muscle.

Topics: AMP-Activated Protein Kinases; Animals; Biological Transport; Blood Glucose; Cells, Cultured; Curcumin; Deoxyglucose; Diet, High-Fat; Enzyme Activation; Glucose; Glucose Transporter Type 4; Hyperglycemia; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal; Obesity; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats; RNA Interference; RNA, Small Interfering; Styrenes

Obesity is strongly associated with the cause of structural and functional changes of the heart in both human and animal models. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiac disorders. Curcumin is a natural product from Curcuma Longa with multiple bioactivities. In our previous study, in order to reach better anti-inflammatory and anti-oxidant dual activities, we designed a new mono-carbonyl curcumin analog, Y20, via the structural modification with both trifluoromethyl and bromine. This study was designed to investigate the protective effects of Y20 on obesity-induced cardiac injury and its underlying mechanisms. In high fat diet-fed rats, oral administration of Y20 at 20 mg/kg or curcumin at 50 mg/kg significantly decreased the cardiac inflammation and oxidative stress and eventually improved the cardiac remodeling by mitigating cardiac disorganization, hypertrophy, fibrosis and apoptosis. Y20 at 20 mg/kg showed comparable and even stronger bioactivities than curcumin at 50 mg/kg. The beneficial actions of Y20 are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation. Taken together, these results suggest that Y20 may have a great therapeutic potential in the treatment of obesity-induced cardiac injury using Nrf2 and NF-κB as the therapeutic targets for treating obesity-related disorders.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Cardiomegaly; Curcumin; Diet, High-Fat; Dietary Fats; Fibrosis; Gene Expression Regulation; Heart; Male; NF-E2-Related Factor 2; NF-kappa B; Obesity; Oxidative Stress; Rats; Rats, Wistar; Ventricular Remodeling

The use of biocompounds as agents with potential anti-obesity effects might be a feasible alternative to the prescription of traditional drugs in the near future. The goal of the present study was to screen five different compounds in relation to their ability to prevent body weight gain and ameliorate obesity-associated metabolic impairments, namely insulin resistance. For this purpose, seventy Wistar rats were randomly assigned into seven experimental groups. A standard diet-fed control group (control, n=10); a high-fat, high-sucrose diet-fed group (HFS, n=10) and five experimental groups which were fed the HFS diet supplemented with one of the following biocompounds; curcumin (100 mg/kg bw, n=10), chlorogenic acid (50 mg/kg bw, n=10), coumaric acid (100 mg/kg bw, n=10), naringin (100 mg/kg bw, n=10) and leucine (1% of diet, n=10). These results confirm the effectiveness of all the compounds to reduce significantly food efficiency, despite the significant higher food intake. Moreover, visceral fat mass percentage was significantly decreased after naringin and coumaric acid supplementation. In fact, this finding might be related to the considerable amelioration of HOMA-IR index detected in naringin-treated animals. A significant reduction in serum insulin levels and an improvement in the intraperitoneal glucose tolerance test and AUC were found in leucine- and coumaric acid-treated rats, respectively. In summary, the tested biocompounds, particularly naringin, coumaric acid and leucine, showed potential benefits in the prevention of obesity-related complications in rats, at least at the proved doses.

Topics: Animals; Blood Glucose; Chlorogenic Acid; Coumaric Acids; Curcumin; Diet, High-Fat; Dietary Fats; Dietary Supplements; Flavanones; Humans; Insulin Resistance; Leucine; Male; Obesity; Rats; Rats, Wistar; Sucrose

Dietary curcumin was studied for its potential to decrease adiposity and reverse obesity- associated cognitive impairment in a mouse model of midlife sedentary obesity. We hypothesized that curcumin intake, by decreasing adiposity, would improve cognitive function in a manner comparable to caloric restriction (CR), a weight loss regimen. 15-month-old male C57BL/6 mice were assigned in groups to receive the following dietary regimens for 12 weeks: (i) a base diet (Ain93M) fed ad libitum (AL), (ii) the base diet restricted to 70% of ad libitum (CR) or (iii) the base diet containing curcumin fed AL (1000 mg/kg diet, CURAL). Blood markers of inflammation, interleukin 6 (IL-6) and C-reactive protein (CRP), as well as an indicator of redox stress (GSH: GSSG ratio), were determined at different time points during the treatments, and visceral and subcutaneous adipose tissue were measured upon completion of the experiment. After 8 weeks of dietary treatment, the mice were tested for spatial cognition (Morris water maze) and cognitive flexibility (discriminated active avoidance). The CR group showed significant weight loss and reduced adiposity, whereas CURAL mice had stable weight throughout the experiment, consumed more food than the AL group, with no reduction of adiposity. However, both CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and GSH as well as the GSH: GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. The results suggest that, independent of their effects on adiposity; dietary curcumin and caloric restriction have positive effects on frontal cortical functions that could be linked to anti-inflammatory or antioxidant actions.

Topics: Adiposity; Animals; Anti-Inflammatory Agents; C-Reactive Protein; Caloric Restriction; Curcumin; Disease Models, Animal; Glutathione; Humans; Inflammation; Interleukin-6; Male; Maze Learning; Mice; Obesity

Adipocyte lipid accumulation due to impaired fatty acid oxidation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. The aim of this study was to determine the antiobesity effects of the herbal composition Gambigyeongsinhwan (4) (GGH(4)) composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata.. The effects of GGH(4) and the individual components on lipid accumulation in 3T3-L1 adipocytes and body weight gain in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined using Oil red O staining, hematoxylin and eosin staining, quantitative real-time PCR, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay.. GGH(4), individual components, and an active principle of Curcuma longa curcumin inhibited lipid accumulation and mRNA levels of adipocyte-specific genes (PPARγ, aP2, and C/EBPα) in 3T3-L1 adipocytes compared with control cells. Treatment with GGH(4), the individual components or curcmumin increased mRNA levels of mitochondrial (CPT-1, MCAD, and VLCAD) and peroxisomal (ACOX and thiolase) PPARα target genes. GGH(4) and the individual components also increased PPARα reporter gene expression compared with control cells. These effects were most prominent in GGH(4)-treated cells. However, the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on adipogenesis. An in vivo study showed that GGH(4) decreased body weight gain, adipose tissue mass, and visceral adipocyte size with increasing mRNA levels of adipose tissue PPARα target genes in OLETF rats.. These results demonstrate that GGH(4) has an antiobesity effects through the inhibition of adipocyte lipid accumulation, and this process may be mediated in part through adipose PPARα activation.

Topics: 3T3-L1 Cells; Alnus; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Proteins; Curcuma; Drugs, Chinese Herbal; Fatty Acid-Binding Proteins; Lipid Metabolism; Male; Medicine, Korean Traditional; Mice; Obesity; Oxazoles; Phytotherapy; Plant Extracts; Plant Preparations; PPAR alpha; PPAR gamma; Rats, Inbred OLETF; RNA, Messenger; Triglycerides; Tyrosine; Weight Gain

Topics: Animals; Curcumin; Fatty Liver; Male; Obesity

Type 2 diabetes is growing at epidemic proportions, and pharmacological interventions are being actively sought. This study examined the effect of a novel neuroprotective curcuminoid, CNB-001 [4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl)vinyl)-2-methoxy-phenol], on glucose intolerance and insulin signaling in high-fat diet (HFD)-fed mice. C57BL6 mice (5-6 weeks old) were randomly assigned to receive either a HFD (45% fat) or a low-fat diet (LFD, 10% fat) for 24 weeks, together with CNB-001 (40 mg/kg i.p. per day). Glucose tolerance test revealed that the area under the curve of postchallenge glucose concentration was elevated on HF-feeding, which was attenuated by CNB-001. CNB-001 attenuated body weight gain, serum triglycerides, and IL-6, and augmented insulin signaling [elevated phosphoprotein kinase B (p-Akt), and phosphoinsulin receptor (p-IR)β, lowered endoplasmic reticulum (ER) stress, protein-tyrosine phosphatase 1B (PTP1B)] and glucose uptake in gastrocnemius muscle of HFD-fed mice. Respiratory quotient, measured using a metabolic chamber, was elevated in HFD-fed mice, which was unaltered by CNB-001, although CNB-001 treatment resulted in higher energy expenditure. In cultured myotubes, CNB-001 reversed palmitate-induced impairment of insulin signaling and glucose uptake. Docking studies suggest a potential interaction between CNB-001 and PTP1B. Taken together, CNB-001 alleviates obesity-induced glucose intolerance and represents a potential candidate for further development as an antidiabetic agent.

Topics: Adiposity; Animals; Catalytic Domain; Cell Line; Cell Survival; Curcumin; Dietary Fats; Endoplasmic Reticulum Stress; Energy Metabolism; Fatty Liver; Glucose Intolerance; Hypoglycemic Agents; Insulin Resistance; Male; Mice, Inbred C57BL; Molecular Docking Simulation; Muscle Fibers, Skeletal; Muscle, Skeletal; Neuroprotective Agents; Obesity; Palmitic Acid; Protein Binding; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Pyrazoles; Signal Transduction; Weight Gain

Fetuin-A is synthesized in the liver and is secreted into the bloodstream. Clinical studies suggest involvement of fetuin-A in metabolic disorders such as visceral obesity, insulin resistance, diabetes, and fatty liver. Curcumin is extracted from the rhizome Curcuma longa and has been shown to possess potent antioxidant, anticarcinogenic, anti-inflammatory, and hypoglycemic properties. In this study, we investigated the effect of curcumin treatment on serum fetuin-A levels as well as hepatic lipids and prooxidant-antioxidant status in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats were divided into six groups. Group 1 was fed control diet (10 % of total calories from fat). Groups 2 and 3 were given curcumin (100 and 400 mg/kg bw/day, respectively ) by gavage for 8 weeks and were fed control diet. Group 4 was fed with HFD (60 % of total calories from fat). Groups 5 and 6 received HFD together with the two doses of curcumin, respectively. Curcumin treatment appeared to be effective in reducing liver triglycerides and serum fetuin-A levels. These findings suggest that the reduction of fetuin-A may contribute to the beneficial effects of curcumin in the pathogenesis of obesity.

Topics: Administration, Oral; alpha-2-HS-Glycoprotein; Animals; Antioxidants; Blood Glucose; Cholesterol; Curcumin; Diet, High-Fat; Dietary Fats; Energy Metabolism; Fatty Liver; Insulin; Liver; Male; Malondialdehyde; Obesity; Rats; Rats, Sprague-Dawley; Triglycerides

Curcumin is a well-known component of traditional turmeric (Curcuma longa), which has been reported to prevent obesity and diabetes. However, the effect of curcumin on hepatic lipid metabolism remains unclear. The aim of this study was to examine the effects of curcumin on hepatic steatosis in high-fat/cholesterol diet (HFD)-induced obese mice. Male C57BL/6J mice were fed a normal diet (ND), HFD or HFD with 0.15% curcumin (HFD+C) for 11 weeks. We found that curcumin significantly lowered the body-weight and adipose tissue weight of mice in the HFD+C group compared with the findings for the HFD group (p < 0.05). The levels of total cholesterol, fasting glucose and insulin in serum were decreased, and HFD-induced impairment of insulin sensitivity was improved by curcumin supplementation (p < 0.05). Curcumin protected against the development of hepatic steatosis by reducing hepatic fat accumulation. Moreover, curcumin activated AMP-activated protein kinase (AMPK) and elevated the gene expression of peroxisome proliferator-activated receptor alpha. By contrast, curcumin suppressed the HFD-mediated increases in sterol regulatory element-binding protein-1, acetyl-CoA carboxylase 1, fatty acid synthase and cluster of differentiation 36 expression. Taken together, these findings indicate that curcumin attenuates HFD-induced hepatic steatosis by regulating hepatic lipid metabolism via AMPK activation, suggesting its use as a therapeutic for hepatic steatosis.

Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Blood Glucose; Body Weight; Cholesterol; Curcumin; Diet, High-Fat; Disease Models, Animal; Fatty Liver; Gene Expression; Insulin; Male; Mice; Mice, Inbred C57BL; Obesity; PPAR alpha

Oxidative stress plays a key role in obesity and diabetes-related mitochondrial dysfunction. Mitochondrial dysfunction is characterized by increased oxidative damage, nitric oxide (NO) synthesis, and a reduced ratio of adenosine-5'-triphosphate (ATP) production/oxygen consumption. Curcumin represents a potential antioxidant and anti-inflammatory agent. In this study, our objective was to determine the effect of curcumin treatment on oxidative stress and mitochondrial dysfunction in high-fat diet (HFD)-induced obese mice (OM). These results suggest that curcumin treatment increased oxygen consumption and significantly decreased lipid and protein oxidation levels in liver mitochondria isolated from HFD-induced OM compared with those in the untreated OM (UOM). In kidney mitochondria, curcumin treatment significantly increased oxygen consumption and decreased lipid and protein peroxidation levels in HFD-induced OM when compared with those in UOM. Curcumin treatment neither has any effect on body weight gain nor have any effects on mitochondrial NO synthesis. These findings suggest that obesity induces oxidative stress and mitochondrial dysfunction, whereas curcumin may have a protective role against obesity-induced oxidative stress and mitochondrial dysfunction.

Topics: Animals; Antioxidants; Curcumin; Diet, High-Fat; Kidney; Liver; Male; Mice; Mice, Obese; Mitochondria, Liver; Molecular Structure; Nitric Oxide; Obesity; Oxidation-Reduction; Oxidative Stress

Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity.. Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation.. These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition.

Topics: Animals; Blood Glucose; Cell Movement; Curcuma; Curcumin; Cytokines; Diet, High-Fat; Dietary Fats; Dietary Supplements; Inflammation; Insulin; Leukocytes; Male; Mice; Mice, Inbred C57BL; Microbiota; Obesity; Piper nigrum; Plant Extracts; Subcutaneous Fat; Weight Gain

Obesity leads to the activation of pro-inflammatory pathways, resulting in a state of low-grade inflammation. Recently, several studies have shown that the exposure to lipopolysaccharide (LPS) could initiate and maintain a chronic state of low-grade inflammation in obese people. As the daily intake of food additives has increased substantially, the aim of the present study was to investigate a potential influence of food additives on the release of leptin, IL-6 and nitrite in the presence of LPS in murine adipocytes. Leptin, IL-6 and nitrite concentrations were analysed in the supernatants of murine 3T3-L1 adipocytes after co-incubation with LPS and the food preservatives, sodium sulphite (SS), sodium benzoate (SB) and the spice and colourant, curcumin, for 24 h. In addition, the kinetics of leptin secretion was analysed. A significant and dose-dependent decrease in leptin was observed after incubating the cells with SB and curcumin for 12 and 24 h, whereas SS decreased leptin concentrations after 24 h of treatment. Moreover, SS increased, while curcumin decreased LPS-stimulated secretion of IL-6, whereas SB had no such effect. None of the compounds that were investigated influenced nitrite production. The food additives SS, SB and curcumin affect the leptin release after co-incubation with LPS from cultured adipocytes in a dose- and time-dependent manner. Decreased leptin release during the consumption of nutrition-derived food additives could decrease the amount of circulating leptin to which the central nervous system is exposed and may therefore contribute to an obesogenic environment.

Topics: 3T3-L1 Cells; Adipocytes, White; Animals; Antioxidants; Appetite Regulation; Cell Survival; Curcumin; Down-Regulation; Food Additives; Food Preservatives; Interleukin-6; Kinetics; Leptin; Lipopolysaccharides; Mice; Nitric Oxide; Obesity; Sodium Benzoate; Sulfites

Obesity-related metabolic abnormalities include a state of chronic inflammation and adipocytokine imbalance, which increase the risk of colon cancer. Curcumin, a component of turmeric, exerts both cancer preventive and antiinflammatory properties. Curcumin is also expected to have the ability to reverse obesity-related metabolic derangements. The present study examined the effects of curcumin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Feeding with a diet containing 0.2% and 2.0% curcumin caused a significant reduction in the total number of colonic premalignant lesions compared with basal diet-fed mice. The expression levels of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 (COX-2) mRNAs on the colonic mucosa of AOM-treated mice were significantly decreased by curcumin administration. Dietary feeding with curcumin markedly activated AMP-activated kinase, decreased the expression of COX-2 protein, and inhibited nuclear factor-κB activity on the colonic mucosa of AOM-treated mice. Curcumin also increased the serum levels of adiponectin while conversely decreasing the serum levels of leptin and the weights of fat. In conclusion, curcumin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model, at least in part, by attenuating chronic inflammation and improving adipocytokine imbalance. Curcumin may be useful in the chemoprevention of colorectal carcinogenesis in obese individuals.

Topics: Adiponectin; Adipose Tissue; AMP-Activated Protein Kinase Kinases; Animals; Anticarcinogenic Agents; Azoxymethane; Colon; Colonic Neoplasms; Curcumin; Cyclooxygenase 2; Dietary Supplements; Interleukin-6; Intestinal Mucosa; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; NF-kappa B; Obesity; Organ Size; Precancerous Conditions; Protein Kinases; Tumor Necrosis Factor-alpha

Obesity is frequently associated with breast cancer. Such associations are possibly mediated by adipokines. Visfatin, an adipokine, has recently been shown to be related to the development and progression of breast cancer. Therefore, the down-regulation of visfatin may be a novel strategy for breast cancer therapy. Curcumin has anticancer activities by modulating multiple signaling pathways and genes. The purpose of this study was to investigate whether visfatin gene expression is affected by curcumin in human breast cancer cells and to characterize the functional role of visfatin in breast cancer. We found that the mRNA and protein levels of visfatin were down-regulated by curcumin in MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cells, along with decreased activity of constitutive nuclear factor (NF)-κB. We confirmed the repressive effect of curcumin on visfatin transcription by performing a visfatin promoter-driven reporter assay and identified two putative NF-κB-binding sites on visfatin promoter that are important for this effect. EMSA and chromatin immunoprecipitation analysis indicated the binding of p65 to the visfatin promoter, which was effectively blocked by curcumin. Enforced expression of p65 protein increased visfatin promoter activity, whereas blocking NF-κB signaling suppressed visfatin gene expression. Visfatin could enhance the invasion of MDA-MB-231 cells and also attenuate curcumin-induced inhibition of cell invasion; on the other hand, visfatin knockdown by small interfering RNA led to the reduction of cell invasion. Our data demonstrate, for the first time, that curcumin down-regulates visfatin gene expression in human breast cancer cells by a mechanism that is, at least in part, NF-κB dependent and suggest that visfatin may contribute to breast cancer cell invasion and link obesity to breast cancer development and progression.

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Curcumin; Cytokines; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; NF-kappa B; Nicotinamide Phosphoribosyltransferase; Obesity; Promoter Regions, Genetic; Response Elements

Mechanisms underlying the attenuation of body weight gain and insulin resistance in response to high fat diet (HFD) by the curry compound curcumin need to be further explored. Although the attenuation of the inflammatory pathway is an accepted mechanism, a recent study suggested that curcumin stimulates Wnt signaling pathway and hence suppresses adipogenic differentiation. This is in contrast with the known repressive effect of curcumin on Wnt signaling in other cell lineages.. We conducted the examination on low fat diet, or HFD fed C57BL/6J mice with or without curcumin intervention for 28 weeks. Curcumin significantly attenuated the effect of HFD on glucose disposal, body weight/fat gain, as well as the development of insulin resistance. No stimulatory effect on Wnt activation was observed in the mature fat tissue. In addition, curcumin did not stimulate Wnt signaling in vitro in primary rat adipocytes. Furthermore, curcumin inhibited lipogenic gene expression in the liver and blocked the effects of HFD on macrophage infiltration and the inflammatory pathway in the adipose tissue.. We conclude that the beneficial effect of curcumin during HFD consumption is mediated by attenuating lipogenic gene expression in the liver and the inflammatory response in the adipose tissue, in the absence of stimulation of Wnt signaling in mature adipocytes.

Topics: Adipocytes; Adipose Tissue; Adiposity; Animals; Curcumin; Dietary Fats; Dietary Supplements; Gene Expression Regulation; Glucose; Hep G2 Cells; Humans; Inflammation; Insulin; Insulin Resistance; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction; Time Factors; Weight Gain

Obesity contributes to the increased risk of liver- related morbidity and mortality. The accumulation of macrophages in adipose tissue in an inflammatory state is a hallmark of obesity-induced hepatic steatosis. In this study, we reveal the role of curcumin in the molecular mechanisms underlying inflammatory events in a model consisting of obese mice with hepatic steatosis. Obese mice fed with curcumin experienced significant weight loss and significantly reduced serum triglyceride (TG) levels. The adipose tumor necrocis factor-α, interleukin-6 (IL-6) and monocyte chemotactic protein-1 levels were significantly higher in obese mice compared to mice fed with curcumin. Compared to the obese mice, curcumin decreased the number of F4/80-positive macrophages in epididymal adipose and liver tissue. The induction of signal transducer and activator of transcription 3 phosphorylation by curcumin resulted in the downregulation of the suppressor of cytokine signaling 3 in the liver of obese mice. Curcumin decreased hepatic TG in obese mice by downregulating the gene expression of sterol regulatory element-binding protein-1c in the liver. The hepatic expression of several mitochondrial biogenesis genes decreased in the obese mice, including mitochondrial DNA (mtDNA), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam), which are responsible for the lower mitochondrial respiratory chain (MRC) complex I activity and adenosine triphosphate production. By contrast, obese mice treated with curcumin showed normalized mtDNA, NRF1 and Tfam gene expression, reduced hepatic nuclear factor-κB activities and levels of thiobarbituric acid reactive substances (TBARS) and restored mitochondrial oxidative metabolism and biogenesis. The results from the present sudy show that curcumin prevents fatty liver disease through multiple mechanisms, and suggest that curcumin may be used to prevent the development and progression of non-alcoholic fatty liver disease (NAFLD).

Topics: Adipose Tissue; Animals; Body Weight; Curcumin; Cytokines; Fatty Liver; Gene Expression Regulation; Inflammation; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Non-alcoholic Fatty Liver Disease; Obesity; Signal Transduction

Curcumin, an active component derived from dietary spice turmeric (Curcuma longa), has been demonstrated antihyperglycemic, antiinflammatory and hypocholesterolemic activities in obesity and diabetes. These effects are associated with decreased level of circulating free fatty acids (FFA), however the mechanism has not yet been elucidated. The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNFα) stimulates chronic lipolysis in obesity and type 2 diabetes. In this study, we examined the role of curcumin in inhibiting lipolytic action upon various stimulations in 3T3-L1 adipocytes.. Glycerol release from TNFα or isoproterenol-stimulated 3T3-L1 adipocytes in the absence or presence of curcumin was determined using a colorimetric assay (GPO-Trinder). Western blotting was used to investigate the TNFα-induced phosphorylation of MAPK and perilipin expression. Fatcake and cytosolic fractions were prepared to examine the isoproterenol-stimulated hormone-sensitive lipase translocation.. Treatment with curcumin attenuated TNFα-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and reversing the downregulation of perilipin protein in TNFα-stimulated adipocytes (p<0.05). The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by curcumin (10-20 μM, p<0.05), which was compatible with reduced perilipin phosphorylation(29%, p<0.05) and hormone-sensitive lipase translocation(20%, p<0.05).. This study provides evidence that curcumin acts on adipocytes to suppress the lipolysis response to TNFα and catecholamines. The antilipolytic effect could be a cellular basis for curcumin decreasing plasma FFA levels and improving insulin sensitivity.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Carrier Proteins; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Fatty Acids, Nonesterified; Glycerol; Insulin Resistance; Isoproterenol; Lipase; Lipolysis; Mice; Obesity; Perilipin-1; Phosphoproteins; Phosphorylation; Phytotherapy; Plant Extracts; Tumor Necrosis Factor-alpha

We examined the anti-obesity effect of fermented Curcuma longa L. (turmeric) standardised ethanol extract (FTE) in the C57BL/6J ob/ob mouse model. Mice were fed a chow diet containing FTE (0, 200, or 500 mg kg⁻¹ body weight) for 9 weeks.. Supplementation with FTE significantly reduced body weight gain and retroperitoneal and epididymal adipose tissue weights compared to the ob/ob control group. Additionally, total cholesterol and triglyceride levels in serum and liver were significantly decreased in FTE-200 and FTE-500 groups when compared to those of the ob/ob control group, whereas the high-density lipoprotein-cholesterol level was significantly increased. The levels of serum adiponectin as well as mRNA expression of lipases, such as hormone sensitive lipase and adipose triglyceride lipase, were clearly increased. In primary adipocytes of C57BL/6J mice, FTE treatment caused a significant increase glycerol release and hormone sensitive lipase levels and decreased perilipin A levels.. These results suggest that supplementation of FTE has potent anti-obesity effects by controlling body weight, fat mass, serum lipids, and hepatic lipids. Moreover, FTE could be considered a potential resource for the treatment of obesity through its promotion of lipolysis via the protein kinase A pathway.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Aspergillus oryzae; Carrier Proteins; Cholesterol; Cholesterol, HDL; Curcuma; Dietary Supplements; Disease Models, Animal; Fermentation; Glycerol; Hypolipidemic Agents; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Perilipin-1; Phosphoproteins; Phytotherapy; Plant Extracts; Reference Standards; RNA, Messenger; Sterol Esterase; Triglycerides; Weight Gain

To determine whether and by what mechanism systemic delivery of curcumin-containing liposomes improves insulin resistance in the leptin deficient (ob/ob) mouse model of insulin resistance.. Insulin resistant ob/ob mice with steatosis were injected intraperitoneally with liposome nanoparticles, entrapping the nuclear factor-κB (NF-κB) inhibitor curcumin (curcusomes), and uptake in liver and adipose tissue was determined by flow cytometry. The effects of curcusomes on macrophage NF-κB activation and cytokine production were assessed. Transfer experiments determined the role of hepatic tumor necrosis factor (TNF)/inducible nitric oxide synthase-producing dendritic cells (Tip-DCs) and adipose tissue macrophages (ATMs) in inflammation-induced insulin resistance, determined by homeostatic assessment of insulin resistance.. Phagocytic myeloid cells infiltrating the liver in ob/ob mice had the phenotypic characteristics of Tip-DCs that arise from monocyte precursors in the liver and spleen after infection. Targeting Tip-DCs and ATMs with curcusomes in ob/ob mice reduced NF-κB/RelA DNA binding activity, reduced TNF, and enhanced interleukin-4 production. Curcusomes improved peripheral insulin resistance.. Both hepatic Tip-DCs and ATMs contribute to insulin resistance in ob/ob mice. Curcusome nanoparticles inhibit proinflammatory pathways in hepatic Tip-DCs and ATMs and reverse insulin resistance. Targeting inflammatory DCs is a novel approach for type 2 diabetes treatment.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cytokines; Dendritic Cells; Drug Delivery Systems; Gene Expression Regulation; Insulin Resistance; Leptin; Liposomes; Liver; Macrophages; Mice; Mice, Inbred C57BL; Mice, Obese; Nanoparticles; NF-kappa B; Obesity; RNA, Messenger; Specific Pathogen-Free Organisms; Tissue Distribution

Angiogenesis is necessary for the growth of adipose tissue. Dietary polyphenols may suppress growth of adipose tissue through their antiangiogenic activity and by modulating adipocyte metabolism. We investigated the effect of curcumin, the major polyphenol in turmeric spice, on angiogenesis, adipogenesis, differentiation, apoptosis, and gene expression involved in lipid and energy metabolism in 3T3-L1 adipocyte in cell culture systems and on body weight gain and adiposity in mice fed a high-fat diet (22%) supplemented with 500 mg curcumin/kg diet for 12 wk. Curcumin (5-20 micromol/L) suppressed 3T3-L1 differentiation, caused apoptosis, and inhibited adipokine-induced angiogenesis of human umbilical vein endothelial cells. Supplementing the high-fat diet of mice with curcumin did not affect food intake but reduced body weight gain, adiposity, and microvessel density in adipose tissue, which coincided with reduced expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2. Curcumin increased 5'AMP-activated protein kinase phosphorylation, reduced glycerol-3-phosphate acyl transferase-1, and increased carnitine palmitoyltransferase-1 expression, which led to increased oxidation and decreased fatty acid esterification. The in vivo effect of curcumin on the expression of these enzymes was also confirmed by real-time RT-PCR in subcutaneous adipose tissue. In addition, curcumin significantly lowered serum cholesterol and expression of PPARgamma and CCAAT/enhancer binding protein alpha, 2 key transcription factors in adipogenesis and lipogenesis. The curcumin suppression of angiogenesis in adipose tissue together with its effect on lipid metabolism in adipocytes may contribute to lower body fat and body weight gain. Our findings suggest that dietary curcumin may have a potential benefit in preventing obesity.

Topics: 3T3-L1 Cells; Acetyl-CoA Carboxylase; Adenylate Kinase; Adipocytes; Adipogenesis; Adipokines; Adipose Tissue; Animals; Apoptosis; Cell Differentiation; Curcumin; Diet; Dietary Fats; Endothelial Cells; Humans; Male; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Obesity; Polymerase Chain Reaction; RNA, Messenger; Umbilical Veins; Vascular Endothelial Growth Factor A

We have previously shown that follicle-stimulating hormone receptor haploinsufficient mice undergo early reproductive senescence with alterations in ovarian structures. The objective of this study was to treat aging (7-8 months) +/- follicle-stimulating hormone receptor mice that are destined for reproductive failure with 2 selected antiandrogens, curcumin and flutamide, to counteract deleterious effects of mild hyperandrogenemia on the ovary and metabolism. Both compounds significantly downregulated the expression of ovarian androgen receptor protein and simultaneously reduced cyclooxygenase 2 protein in the ovary. Immunolocalization of bone morphogenetic protein-15 in the ovary was enhanced considerably by curcumin and partially by flutamide in treated mice. Improved structural changes were evident in zona pellucida of curcumin-treated ovaries. Flutamide reduced p450c-17 (cyp-17 protein) enzyme expression in thecal/interstitial cells, whereas increased expression of 3beta-hydroxysteroid dehydrogenase in thecal cells and granulosa-lutein cells of big follicles was apparent in curcumin-treated ovaries. Reduction in abdominal adiposity was greater in flutamide-treated mice. Taken together, our study allows the following conclusions: changes in ovarian histology and oocyte components as well as adipose tissue indicate the potential for reversing ovarian decline and metabolism because of mild hyperandrogenemia that occurs with aging in follicle-stimulating hormone receptor haploinsufficienct mice.

Topics: Abdominal Fat; Aging; Animals; Curcumin; Female; Flutamide; Haploidy; Mice; Mice, Transgenic; Obesity; Ovary; Receptors, FSH

To evaluate the insulin and leptin resistance of curcumin on simplicity obesity rats.. All 50 SPF grade healthy Sprague-Dawley male initial weaning rats were used for two groups in stratified sampling by weight: 30 in treated group and 20 in control group. They were assigned to the following treatment for 8 weeks: the treated group was fed with high-fat food and the control group was fed with normal food. Eight weeks later, adiposity model rats were prepared. Groups: adiposity model rats were divided into 3 groups: model + low curcumin (1.25 g/kg), model + high curcumin (5.00 g/kg) and a model group. In addition, there also had a normal control and a control + high curcumin (5.00 g/kg) group. Ten rats in every group and all given ground feed. After intragastric administration in different doses of curcumin 4 weeks, the effects and pathological changes were observed by the blood sugar, insulin, leptin and TNF-alpha, pathology and transmission electron microscope of pancreatic gland.. Given 4 weeks the different dose of curcumin on the simplicity obesity rats, the significant diminished weight (435.0 +/- 37.6) g and content of lipocyte (4.78 +/- 1.87) g as compared with the obesity model control (492.3 +/- 14.8) g and (8.94 +/- 1.88) g (t values were 4.484 and 4.961 respectively, P < 0.01), level of blood sugar (4.50 +/- 0.09) mmol/L, insulin (7.43 +/- 0.65) mmol/L, leptin (3.40 +/- 0.39) mmol/L and TNF-alpha (2.42 +/- 0.19) ng/ml were significantly decreased than those of adiposity model rats (4.94 +/- 0.12) mmol/L, (9.30 +/- 0.21) mmol/L, (4.40 +/- 0.23) mmol/L and (2.86 +/- 0.49) ng/ml (t values were 8.297, 7.743, 6.247 and 2.368 respectively, P < 0.05), and there was no significant difference with the control group (4.30 +/- 0.14) mmol/L on the level of blood sugar (t = 0.399, P > 0.05). There were a lot of secretory granules with large sphere volume in beta cells of pancreatic island found by transmission electron microscope, and these secretory granules had a higher electron density than those in non-disposed groups.. By diminishing the sediment of fat, relaxing the lymphatic return, and refraining the apoptosis of beta cells, the curcumin might significantly decrease the level of insulin resistance and leptin resistance caused by the high fat diet.

Topics: Animals; Apoptosis; Curcumin; Disease Models, Animal; Insulin; Insulin Resistance; Islets of Langerhans; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley

Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. We tested the hypothesis that the plant polyphenolic compound curcumin, which is known to exert potent antiinflammatory and antioxidant effects, would ameliorate diabetes and inflammation in murine models of insulin-resistant obesity. We found that dietary curcumin admixture ameliorated diabetes in high-fat diet-induced obese and leptin-deficient ob/ob male C57BL/6J mice as determined by glucose and insulin tolerance testing and hemoglobin A1c percentages. Curcumin treatment also significantly reduced macrophage infiltration of white adipose tissue, increased adipose tissue adiponectin production, and decreased hepatic nuclear factor-kappaB activity, hepatomegaly, and markers of hepatic inflammation. We therefore conclude that orally ingested curcumin reverses many of the inflammatory and metabolic derangements associated with obesity and improves glycemic control in mouse models of type 2 diabetes. This or related compounds warrant further investigation as novel adjunctive therapies for type 2 diabetes in man.

Topics: Adiponectin; Adipose Tissue, White; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Models, Animal; Gene Expression; Immunohistochemistry; Inflammation; Interleukin-6; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; NF-kappa B; Obesity; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha