cannabidiol and Obesity

Topics: Animals; Cannabidiol; Cannabis; Dronabinol; Hallucinogens; Obesity

Topics: Analgesics; Anti-Inflammatory Agents; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Dronabinol; Humans; Inflammation; Obesity

Currently, an increasing number of diseases related to insulin resistance and obesity is an alarming problem worldwide. It is well-known that the above states can lead to the development of type 2 diabetes, hypertension, and cardiovascular diseases. An excessive amount of triacylglycerols (TAGs) in a diet also evokes adipocyte hyperplasia and subsequent accumulation of lipids in peripheral organs (liver, cardiac muscle). Therefore, new therapeutic methods are constantly sought for the prevention, treatment and alleviation of symptoms of the above mentioned diseases. Currently, much attention is paid to

Topics: Animals; Anti-Obesity Agents; Cannabidiol; Cannabinoids; Cannabis; Humans; Lipid Metabolism; Obesity; Phytochemicals; Phytotherapy

Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose and lipid metabolism, by exerting pro-apoptotic effects in pancreatic beta cells and by facilitating inflammation in pancreatic islets. Furthermore, hyperglycaemia associated with diabetes has also been implicated in triggering perturbations of the ECS amplifying the pathological processes mentioned above, eventually culminating in a vicious circle. Compelling evidence from preclinical studies indicates that the ECS also influences diabetes-induced oxidative stress, inflammation, fibrosis and subsequent tissue injury in target organs for diabetic complications. In this review, we provide an update on the contribution of the ECS to the pathogenesis of diabetes and diabetic microvascular (retinopathy, nephropathy and neuropathy) and cardiovascular complications. The therapeutic potential of targeting the ECS is also discussed.. This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cannabidiol; Chronic Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Endocannabinoids; Humans; Insulin Resistance; Insulin-Secreting Cells; Obesity; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2

Cannabidiol, a cannabinoid and serotonin receptor antagonist, may alleviate hyperphagia without the side effects of rimonabant (for example depression and reduced insulin sensitivity). Similar to the peroxisome proliferator-activated receptor-gamma agonists, it may also help the differentation of adipocytes. Cannabidiol has an immunomodulating effect, as well, that helps lessen the progression of atherosclerosis induced by high glucose level. It may also be effective in fighting ischaemic diseases, the most harmful complications of metabolic syndrome. However, it can only be administered as an adjuvant therapy because of its low binding potency, and its inhibiting effect of cytochrome P450 enzymes should also be considered. Nevertheless, it may be beneficially used in adjuvant therapy because of its few side effects.

Topics: Adipocytes; Appetite Depressants; Atherosclerosis; Cannabidiol; Cannabinoid Receptor Antagonists; Disease Progression; Humans; Hyperphagia; Ischemia; Metabolic Syndrome; Obesity; Piperidines; PPAR gamma; Pyrazoles; Rimonabant

The study explored the potential protective influence of cannabidiol (CBD) on myocardial inflammation state, with a special focus on arachidonic acid (AA), and oxidative balance in lipid overload conditions. The 7-week experiment was conducted on male Wistar rats receiving standard or high-fat diet (HFD) with intraperitoneal CBD injections for the last 14 days. The n-3 and n-6 polyunsaturated fatty acids (PUFAs) activities and AA concentration in selected fractions were evaluated by gas-liquid chromatography (GLC). The expression of proteins was determined by Western blot and the concentration of different parameters by ELISA, colorimetric, or multiplex assay kits. Our results revealed that CBD increased n-3 PUFAs activity in phospholipid and triacylglycerol fractions, and decreased AA content in the HFD group, especially in the phospholipid pool. Simultaneously, CBD decreased the expression of nuclear factor kappa B, cyclooxygenase-1, and - 2, resulting in the reduction of prostaglandin E2 and the increment of prostaglandin I2. CBD appears to be relatively safe for the treatment of obesity-induced heart disease, as it has anti-inflammatory and partially antioxidative properties.

Topics: Animals; Arachidonic Acid; Cannabidiol; Fatty Acids, Omega-6; Male; Obesity; Phospholipids; Rats; Rats, Wistar

Topics: Animals; Cannabidiol; Cannabis; Dronabinol; Endocannabinoids; Glucose; Mice; Mice, Inbred C57BL; Obesity; Weight Gain

It is known that metabolic disturbances, including obesity, predispose to an increased incidence of cardiovascular diseases. Elevated consumption of dietary fat results in intramyocardial accumulation of lipids and their biologically active derivatives, which can disrupt the contractile function of the heart, its metabolism, and intracellular signaling pathways. Therefore, alternative methods, such as phytocannabinoids, are being sought for the treatment of obesity-related effects. In a model of rodent obesity (seven weeks of high-fat-diet (HFD) regime), we used cannabidiol-CBD therapy (intraperitoneal injections for 14 days; 10 mg/kg). High-performance and gas-liquid chromatographies were applied in order to determine sphingolipids in the heart and plasma as well as Western blotting for protein expression. Two-week CBD administration significantly inhibited the de novo ceramide synthesis pathway in the heart of HFD fed rats by lowering sphinganine and sphinganine-1-phosphate contents. The above reductions were accompanied by markedly diminished expressions of myocardial serine palmitoyltransferase 1 and 2 as well as ceramide synthase 5 and 6 in the HFD group with 2-week CBD treatment. To our knowledge, this research is the first that reveals unknown effects of CBD treatment on the heart, i.e., amelioration of de novo ceramide synthesis pathway in obese rats.

Topics: Animals; Biosynthetic Pathways; Cannabidiol; Ceramides; Diet, High-Fat; Disease Models, Animal; Down-Regulation; Insulin; Insulin Resistance; Lipid Metabolism; Lipogenesis; Male; Muscle, Skeletal; Myocardium; Obesity; Rats; Rats, Wistar; Serine C-Palmitoyltransferase; Sphingolipids; Sphingosine

The excessive consumption of ultra-processed foods and the development of obesity has been associated with several comorbidities, including psychiatric disorders. Excess fat tissue promotes a low-intensity inflammatory state, mainly in the white tissue, which is essential in developing metabolic alterations and influences brain homeostasis. In this scenario, Cannabidiol (CBD), a compound from Cannabis sativa, has presented anxiolytic and anti-inflammatory effects in murine models. This study verified whether CBD treatment would ameliorate the compulsive-like and anxiety-like behaviors observed after mice's chronic consumption of a high-refined carbohydrate (HC) diet. BALB/c male mice received a control or HC diet for 12 weeks followed by vehicle and CBD (30 mg/Kg, i.p.) administration, and their behavior was evaluated in the Marble Burying test (MB) and Novel Suppressing Feeding test (NSF). The sub-chronic, but not acute, treatment with CBD attenuated the compulsive-like and anxiogenic-like behavior induced by the HC diet. Our data reinforced the harmful effects of the HC diet's chronic consumption on compulsive and anxious behaviors and the potential of CBD as a drug treatment for psychiatric disorders associated with obesity.

Topics: Animals; Cannabidiol; Carbohydrates; Compulsive Behavior; Male; Mice; Mice, Inbred BALB C; Obesity

The consumption of fatty acids has increased drastically, exceeding the nutritional requirements of an individual and leading to numerous metabolic disorders. Recent data indicate a growing interest in using cannabidiol (CBD) as an agent with beneficial effects in the treatment of obesity. Therefore, our aim was to investigate the influence of chronic CBD administration on the n-6/n-3 polyunsaturated fatty acids (PUFAs) ratio in different lipid fractions, inflammatory pathway and oxidative stress parameters in the white and red gastrocnemius muscle. All the designed experiments were performed on Wistar rats fed a high-fat diet (HFD) or a standard rodent diet for seven weeks and subsequently injected with CBD (10 mg/kg once daily for two weeks) or its vehicle. Lipid content and oxidative stress parameters were assessed using gas-liquid chromatography (GLC), colorimetric and/or immunoenzymatic methods, respectively. The total expression of proteins of an inflammatory pathway was measured by Western blotting. Our results revealed that fatty acids (FAs) oversupply is associated with an increasing oxidative stress and inflammatory response, which results in an excessive accumulation of FAs, especially of n-6 PUFAs, in skeletal muscles. We showed that CBD significantly improved the n-6/n-3 PUFA ratio and shifted the equilibrium towards anti-inflammatory n-3 PUFAs, particularly in the red gastrocnemius muscle. Additionally, CBD prevented generation of lipid peroxidation products and attenuated inflammatory response in both types of skeletal muscle. In summary, the results mentioned above indicate that CBD presents potential therapeutic properties with respect to the treatment of obesity and related disturbances.

Topics: Animals; Cannabidiol; Cannabis; Diet, High-Fat; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Inflammation; Insulin Resistance; Lipid Metabolism; Lipid Peroxidation; Lipids; Male; Muscle, Skeletal; Obesity; Oxidative Stress; Rats; Rats, Wistar

Obesity-related insulin resistance (IR) and attenuated brain insulin signaling are significant risk factors for neurodegenerative disorders, e.g., Alzheimer's disease. IR and type 2 diabetes correlate with an increased concentration of sphingolipids, a class of lipids that play an essential structural role in cellular membranes and cell signaling pathways. Cannabidiol (CBD) is a nonpsychoactive constituent of Cannabis sativa plant that interacts with the endocannabinoidome. Despite known positive effects of CBD on improvement in diabetes and its aftermath, e.g., anti-inflammatory and anti-oxidant effects, there are no studies evaluating the effect of phytocannabinoids on the brain insulin resistance and sphingolipid metabolism. Our experiment was carried out on Wistar rats that received a high-fat diet and/or intraperitoneal CBD injections. In our study, we indicated inhibition of de novo synthesis and salvage pathways, which resulted in significant changes in the concentration of sphingolipids, e.g., ceramide and sphingomyelin. Furthermore, we observed reduced brain IR and decreased tau protein phosphorylation what might be protective against neuropathologies development. We believe that our research will concern a new possible therapeutic approach with Cannabis -plant derived compounds and within a few years, cannabinoids would be considered as prominent substances for targeting both metabolic and neurodegenerative pathologies.

Topics: Animals; Brain; Cannabidiol; Ceramides; Cerebral Cortex; Diabetes Mellitus, Experimental; Diet, High-Fat; Insulin; Insulin Resistance; Lipid Metabolism; Male; Neurodegenerative Diseases; Neuroprotective Agents; Obesity; Phosphorylation; Rats, Wistar; Receptors, Cannabinoid; Signal Transduction; Sphingolipids; Sphingomyelins; tau Proteins

O-1602 and O-1918 are atypical cannabinoid ligands for GPR55 and GPR18, which may be novel pharmaceuticals for the treatment of obesity by targeting energy homeostasis regulation in skeletal muscle. This study aimed to determine the effect of O-1602 or O-1918 on markers of oxidative capacity and fatty acid metabolism in the skeletal muscle. Diet-induced obese (DIO) male Sprague Dawley rats were administered a daily intraperitoneal injection of O-1602, O-1918 or vehicle for 6 weeks. C

Topics: Adaptor Proteins, Signal Transducing; Adult; Animals; Anisoles; Cannabidiol; Cell Line; Cells, Cultured; Cyclohexanes; Fatty Acids; Female; Homeostasis; Humans; Male; Mice; Middle Aged; Muscle, Skeletal; NFATC Transcription Factors; Obesity; PPAR gamma; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled

Topics: Animals; Blood Glucose; Cannabidiol; Ceramides; Diet, High-Fat; Disease Models, Animal; Endocannabinoids; Glycogen; Insulin; Insulin Resistance; Male; Metabolic Networks and Pathways; Muscle, Skeletal; Obesity; Rats; Rats, Wistar; Signal Transduction; Sphingolipids

Topics: Adipogenesis; Adiposity; Animals; Biomarkers; Body Composition; Cannabidiol; Cell Differentiation; Diet, High-Fat; Feeding Behavior; Fibroblast Growth Factors; HEK293 Cells; Hormones; Humans; Insulin Resistance; Male; Mice, Inbred C57BL; Obesity; Osteoblasts; PPAR gamma; Weight Gain