piperine and Insulin-Resistance

This randomized, double blind, placebo-controlled, 8 week trial assessed the efficacy on metabolic changes produced by a consumption of a combination of bioactive food ingredients (epigallocatechin gallate, capsaicins, piperine and L-carnitine) versus a placebo, as part of a therapeutic 'lifestyle change' diet, in 86 overweight subjects. Forty-one patients (2/14 F/M; age 43.7 ± 8.5; BMI 30.3 ± 3.5 kg/m(2)) were randomized to the supplemented group and 45 (29/16; age 40.7 ± 10.2; BMI 30.0 ± 2.7) to the control group. We observed that consumption of the dietary supplement was associated with a significantly greater decrease in insulin resistance, assessed by homostasis model assessment (p < 0.001), leptin/adiponectin ratio (p < 0.04), respiratory quotient (p < 0.008). LDL-cholesterol levels (p < 0.01). Moreover, statistically significant differences were recorded between the two groups in relation to urinary norepinephrine levels (p < 0.001). Leptin, ghrelin, C-reactive protein decreased and resting energy expenditure increased significantly in the supplemented group (p < 0.05, 0.03, 0.02 and 0,02 respectively), but not in the placebo group; adiponectin decreased significantly in the placebo group (0.001) but not in the supplemented group, although no statistical significance between the groups was elicited. BMI, fat mass (assessed by DXA) and vascular endothelial growth factor significantly decreased, whilst the resting energy expenditure/free fat mass significantly increased in both groups. In general, a greater change was recorded in the supplemented group compared to the placebo, although no statistically significant difference between the two groups was recorded. These results suggest that the combination of bioactive food ingredients studied might be useful for the treatment of obesity-related inflammatory metabolic dysfunctions.

Topics: Adipokines; Adult; Alkaloids; Benzodioxoles; Capsaicin; Carnitine; Catechin; Diet, Reducing; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation Mediators; Insulin Resistance; Male; Middle Aged; Overweight; Piperidines; Polyunsaturated Alkamides; Time Factors; Weight Loss; Young Adult

The global prevalence of diabetes mellitus is rising, especially in India. Medicinal herbs, whether used alone or in combination with conventional medicines, have shown promise in managing diabetes and improving overall well-being. Piperine (PIP), a major bioactive compound found in pepper, is gaining attention for its beneficial properties. This study aimed to assess whether PIP could alleviate diabetes by targeting insulin pathway-related molecules in the adipose tissue of rats on a high-fat diet (HFD). After 60 days on the HFD, rats received PIP at a dose of 40 mg/kg body weight for one month. The results showed that PIP significantly improved metabolic indicators, antioxidant enzymes, and carbohydrate metabolic enzymes. It also regulated the mRNA and protein expression of insulin signaling, which had been disrupted by the diet and sucrose intake. Molecular docking analysis also revealed strong binding of PIP to key diabetes-related regulatory proteins, including Akt (-6.2 kcal/mol), IR (-7.02 kcal/mol), IRS-1 (-6.86 kcal/mol), GLUT4 (-6.24 kcal/mol), AS160 (-6.28 kcal/mol), and β-arrestin (-6.01 kcal/mol). Hence, PIP may influence the regulation of glucose metabolism through effective interactions with these proteins, thereby controlling blood sugar levels due to its potent antilipidemic and antioxidant properties. In conclusion, our study provides in vivo experimental evidence against the HFD-induced T2DM model for the first time, making PIP a potential natural remedy to enhance the quality of life for diabetic patients and aid in their management.

Topics: Animals; Antioxidants; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Humans; Insulin; Insulin Resistance; Molecular Docking Simulation; Proto-Oncogene Proteins c-akt; Quality of Life; Rats

Substantial evidence suggests that pepper consumption is associated with a reduced risk of obesity-related complications. However, whether piperine, the main component of pepper, improves obesity-induced hepatic lipid accumulation and insulin resistance and the action mechanism of piperine still remain unclear. We hypothesized that piperine attenuates high-fat diet (HFD)-induced obesity and improves the related metabolic complications in HFD-induced obese rats. Adult Sprague-Dawley (SD) male rats were fed a control diet (CON) or an HFD for 16 weeks. Obese rats were divided into 4 groups: HFD and HFD with daily gavage of piperine 2.7 mg/kg body weight (PIP-Low), 13.5 mg/kg body weight (PIP-Medium), and 27 mg/kg body weight (PIP-High) for another 8 weeks. Rats were euthanized after an 8-hour fast, and the liver, heart, kidney, and white adipose tissue were collected and stored at -80 °C. Piperine administration significantly reduced weight gain, plasma insulin, and glucose concentration. For oral piperine at a dose of 27 mg/kg body weight, body weight significantly decreased by 5.7% compared with that in the HFD group. Additionally, oral piperine administration considerably reduced serum triglyceride concentration. Furthermore, piperine administration reversed the HFD-induced downregulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling molecules and increased the plasma levels of adiponectin and the messenger RNA expression of the adiponectin receptor; additionally, it increased the phosphorylation of phosphatidylinositol-3 kinase (PI3K) and protein kinase B. Overall, oral piperine administration reversed HFD-induced liver lipid accumulation and insulin resistance, possibly via the inactivation of adiponectin-AMPK and PI3K-Akt signaling. These findings imply that piperine could serve as an effective agent for healthy weight loss.

Topics: Adiponectin; Animals; Body Weight; Diet, High-Fat; Fatty Liver; Insulin; Insulin Resistance; Lipids; Liver; Male; Obesity; Phosphatidylinositol 3-Kinases; Rats; Rats, Sprague-Dawley

Obesity is one of the major risk factor for cardiovascular and metabolic diseases. A disproportional accumulation of fat at visceral (VAT) compared to subcutaneous sites (SAT) has been suspected as a key detrimental event. We used non-targeted metabolomics profiling to reveal metabolic pathways associated with higher VAT or SAT amount among subjects free of metabolic diseases to identify possible contributing metabolic pathways. The study population comprised 491 subjects [mean (standard deviation): age 44.6 yrs (13.0), body mass index 25.4 kg/m² (3.6), 60.1% females] without diabetes, hypertension, dyslipidemia, the metabolic syndrome or impaired renal function. We associated MRI-derived fat amounts with mass spectrometry-derived metabolites in plasma and urine using linear regression models adjusting for major confounders. We tested for sex-specific effects using interactions terms and performed sensitivity analyses for the influence of insulin resistance on the results. VAT and SAT were significantly associated with 155 (101 urine) and 49 (29 urine) metabolites, respectively, of which 45 (27 urine) were common to both. Major metabolic pathways were branched-chain amino acid metabolism (partially independent of insulin resistance), surrogate markers of oxidative stress and gut microbial diversity, and cortisol metabolism. We observed a novel positive association between VAT and plasma levels of the potential pharmacological agent piperine. Sex-specific effects were only a few, e.g. the female-specific association between VAT and O-methylascorbate. In brief, higher VAT was associated with an unfavorable metabolite profile in a sample of healthy, mostly non-obese individuals from the general population and only few sex-specific associations became apparent.

Topics: Adipose Tissue; Adult; Alkaloids; Ascorbic Acid; Benzodioxoles; Biomarkers; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Insulin Resistance; Intra-Abdominal Fat; Magnetic Resonance Imaging; Male; Metabolic Networks and Pathways; Metabolome; Middle Aged; Organ Size; Piperidines; Polyunsaturated Alkamides; Sex Factors; Subcutaneous Fat

Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M. Newborn mice were subcutaneously (s.c.) injected with monosodium glutamate (MSG) to establish a diabetes model. After 24 weeks, the MSG obese mice were divided into three groups and treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for 10 successive weeks, respectively.. The obesity model was successfully established, as the body weight, insulin resistance, fasting blood glucose (FBG) and dyslipidemia were significantly increased. The 10-week administration of piperine to the obese mice not only significantly decreased the elevated FBG (Model: 6.45 ± 0.41 mM; Piperine: 4.72 ± 0.44 mM, p < 0.01), serum TC (Model: 5.66 ± 0.66 mM; Piperine: 3.55 ± 0.30 mM, p < 0.01) and TG (Model: 1.41 ± 0.08 mM; Piperine: 0.94 ± 0.05 mM, p < 0.001), but also enhanced the glucose infusion rate in the hyperglycemic clamp experiment. Meanwhile, piperine improved glucose intolerance and insulin resistance in MSG obese mice. Piperine markedly decreased the total and differential white blood cell (WBC) count, the serum levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines such as galectin-3 (Gal-3) and interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M. Piperine served as an immunomodulator for the treatment of obesity-related diabetes through its anti-inflammatory effects, which might be achieved by inhibiting macrophages M

Topics: Adipose Tissue; Alkaloids; Animals; Benzodioxoles; Body Weight; Cytochrome P-450 Enzyme Inhibitors; Cytokines; Female; Flavoring Agents; Glucose Intolerance; Inflammation; Insulin Resistance; Macrophages; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Piperidines; Polyunsaturated Alkamides; Sodium Glutamate

To investigate the effect of piperine on the disorder of glucose metabolism in the cell model with insulin resistance (IR) and explore the molecules mechanism on intervening the upstream target of AMPK signaling pathway. The insulin resistance models in HepG2 cells were established by fat emulsion stimulation. Then glucose consumption in culture supernatant was detected by GOD-POD method. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of leptin(LEP) and adiponectin(APN) in culture supernatant; Real-time quantitative PCR was used to assess the mRNA expression of APN and LEP; and the protein expression levels of LepR, AdipoR1, AdipoR2 and the activation of AMPK signaling pathway were detected by Western blot analysis. The results showed that piperine, rosiglitazone and AMPK agonist AICAR could significantly elevate the glucose consumption in insulin resistance cell models, enhance the level of APN, promote APN mRNA transcripts and increase the protein expression of Adipo receptor. Meanwhile,AMPKα mRNA and р-AMPKα protein expressions were also increased in piperine treated cells, but both LEP mRNA expression and LepR protein expressions were decreased in piperine treated group. The results indicated that piperine could significantly ameliorate the glucose metabolism disorder in insulin resistance cell models through regulating upstream molecules (APN and LEP) of AMPK signaling pathway, and thus activate the AMPK signaling pathway.

Topics: Alkaloids; AMP-Activated Protein Kinase Kinases; Benzodioxoles; Glucose; Hep G2 Cells; Humans; Insulin Resistance; Piperidines; Polyunsaturated Alkamides; Protein Kinases; Signal Transduction

This study examined the effect of piperine on hepatic steatosis and insulin resistance induced in mice by feeding a high-fat diet (HFD) for 13 weeks and elucidated potential underlying molecular mechanisms. Administration of piperine (50 mg/kg body weight) to mice with HFD-induced hepatic steatosis resulted in a significant increase in plasma adiponectin levels. Also, elevated plasma concentrations of insulin and glucose and hepatic lipid levels induced by feeding a HFD were reversed in mice when they were administered piperine. However, piperine did not reduce body weight and other biochemical markers to an extent where they became equal to the levels found in the CD-fed mice. Piperine reversed HFD-induced down-regulation of adiponecitn-AMP-activated protein kinase (AMPK) signalling molecules which play an important role in mediating lipogenesis, fatty acid oxidation and insulin signalling in the livers of mice. The expressions of lipogenic target genes were decreased, whereas the expression of carnitine palmitoyltransferase 1 (CPT1) gene involved in fatty acid oxidation was increased in the livers of the Pin50 group. Piperine significantly decreased the phosphorylation of insulin receptor substrate-1 (IRS-1) compared with the HFD-fed mice. Administration of piperine appeared to reverse preexisting HFD-induced hepatic steatosis and insulin resistance, probably by activation of adiponectin-AMPK signalling in mice.

Topics: Adiponectin; Alkaloids; AMP-Activated Protein Kinases; Animals; Benzodioxoles; Diet, High-Fat; Fatty Liver; Humans; Insulin Resistance; Lipogenesis; Male; Mice; Mice, Inbred C57BL; Piper nigrum; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Triglycerides