The endocannabinoid system: a new approach to control cardiovascular disease.

Posted on February 20, 2016 by David

“The endocannabinoid (EC) system consists of 2 types of G-protein-coupled cannabinoid receptors–cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2)–and their natural ligands.

The EC system plays a key role in the regulation of food intake and fat accumulation, as well as glucose and lipid metabolism.

When overactivated, the EC system triggers dyslipidemia, thrombotic and inflammatory states, and insulin resistance.

Blocking CB1 receptors centrally and peripherally in adipose tissue can help normalize an overactivated EC system. CB1 blockade helps regulate food intake and adipose tissue metabolism, contributing to improved insulin sensitivity and other features of the metabolic syndrome.

Visceral adipose tissue is most closely associated with the metabolic syndrome, which is a constellation of conditions that place people at high risk for coronary artery disease.

Targeting the EC system represents a new approach to treating visceral obesity and reducing cardiovascular risk factors.”

http://www.ncbi.nlm.nih.gov/pubmed/16473257

http://www.thctotalhealthcare.com/category/cardiovascular-disease/

Vaccenic acid suppresses intestinal inflammation by increasing the endocannabinoid anandamide and non-cannabinoid signaling molecules in a rat model of the metabolic syndrome.

Posted on February 20, 2016 by David

“Vaccenic acid (VA), the predominant ruminant-derived trans fat in the food chain, ameliorates hyperlipidemia yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (EC) by altering the availability of their biosynthetic precursor, arachidonic acid (AA) in membrane phospholipids (PL).

Interestingly, VA increased jejunal concentrations of anandamide and those of the non-cannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to CD (P<0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase and mRNA expression TNFα and IL-1β (P<0.05).

The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of EC and other non-cannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine.”

http://www.ncbi.nlm.nih.gov/pubmed/26891736

Effects of chronic exercise on the endocannabinoid system in Wistar rats with high-fat diet-induced obesity.

Posted on February 18, 2016 by David

“The endocannabinoid system is dysregulated during obesity in tissues involved in the control of food intake and energy metabolism.

We examined the effect of chronic exercise on the tissue levels of endocannabinoids (eCBs) and on the expression of genes coding for cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) (Cnr1 and Cnr2, respectively) in the subcutaneous (SAT) and visceral adipose tissues and in the soleus and extensor digitorim longus (EDL) muscles, in rats fed with standard or high-fat diet…

The levels of eCBs and Cnr1 expression are altered in a tissue-specific manner following a high-fat diet, and chronic exercise reverses some of these alterations.”

http://www.ncbi.nlm.nih.gov/pubmed/26880264

A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

Posted on February 8, 2016 by David

“The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice.

The eCB system is over-active in human obesity.

Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system.

Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity.

In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.”

http://www.ncbi.nlm.nih.gov/pubmed/26849214

Cannabinoid receptor type 1 mediates high-fat diet-induced insulin resistance by increasing forkhead box O1 activity in a mouse model of obesity.

Posted on February 8, 2016 by David

“Hepatic glucose production is promoted by forkhead box O1 (FoxO1) under conditions of insulin resistance.

The overactivity of cannabinoid receptor type 1 (CB1R) partly causes increased liver fat deposits and metabolic dysfunction in obese rodents by decreasing mitochondrial function.

The aim of the present study was to investigate the role of FoxO1 in CB1R-mediated insulin resistance through the dysregulation of mitochondrial function in the livers of mice with high-fat diet (HFD)-induced obesity.

Taken together, our findings suggest that the anti-insulin resistance effect of AM251, which leads to an improvement of mitochondrial function in hepatic steatosis, is mediated through FoxO1.”

http://www.ncbi.nlm.nih.gov/pubmed/26847930

CB1 receptor blockade counters age-induced insulin resistance and metabolic dysfunction.

Posted on January 14, 2016 by David

“The endocannabinoid system can modulate energy homeostasis by regulating feeding behaviour as well as peripheral energy storage and utilization.

Importantly, many of its metabolic actions are mediated through the cannabinoid type 1 receptor (CB1R), whose hyperactivation is associated with obesity and impaired metabolic function.

Herein, we explored the effects of administering rimonabant, a selective CB1R inverse agonist, upon key metabolic parameters in young (4 month old) and aged (17 month old) adult male C57BL/6 mice…

Collectively, our findings indicate a key role for CB1R in aging-related insulin resistance and metabolic dysfunction and highlight CB1R blockade as a potential strategy for combating metabolic disorders associated with aging.”

http://www.ncbi.nlm.nih.gov/pubmed/26757949

Computational Prediction and Biochemical Analyses of New Inverse Agonists for the CB1 Receptor.

Posted on December 4, 2015 by David

“Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity.

The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 are used here to predict the binding sites for known CB1-selective inverse agonists including rimonabant and its seven known derivatives.

This binding pocket, which differs significantly from previously published models, is used to identify 16 novel compounds expected to be CB1 inverse agonists by exploiting potential new interactions.

We show experimentally that two of these compounds exhibit inverse agonist properties including inhibition of basal and agonist-induced G-protein coupling activity, as well as an enhanced level of CB1 cell surface localization.

This demonstrates the utility of using the predicted binding sites for an ensemble of CB1 receptor structures for designing new CB1 inverse agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/26633590

Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol.

Posted on December 4, 2015 by David

“Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users.

Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice.

THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC.

Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.”

http://www.ncbi.nlm.nih.gov/pubmed/26633823

“Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol… To follow up on our hypothesis that exposure to THC may produce weight loss, in the current study we investigated whether chronic THC inhibits weight gain in lean and diet-induced obese (DIO) mice… We present data showing that chronic administration of the CB1/CB2 receptor partial agonist, THC, prevents weight gain in DIO mice. Furthermore, we show evidence that DIO-mediated modifications in gut microbiota are prevented in chronically THC treated mice… In conclusion, we present data showing the CB1/CB2 receptor partial agonist THC, induces hypophagia and prevents weight gain in obesity and suggest these actions may be mediated in part by modifications of the gut microbiota.” http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144270

The Effect of Medical Marijuana Laws on Body Weight.

Posted on November 28, 2015 by David

“This study is the first to examine the effects of medical marijuana laws (MMLs) on body weight, physical wellness, and exercise.

Using data from the 1990 to 2012 Behavioral Risk Factor Surveillance System and a difference-in-difference approach, we find that the enforcement of MMLs is associated with a 2% to 6% decline in the probability of obesity.

We find some evidence of age-specific heterogeneity in mechanisms. For older individuals, MML-induced increases in physical mobility may be a relatively important channel, while for younger individuals, a reduction in consumption of alcohol, a substitute for marijuana, appears more important.

These findings are consistent with the hypothesis that MMLs may be more likely to induce marijuana use for health-related reasons among older individuals, and cause substitution toward lower-calorie recreational ‘highs’ among younger individuals.

Our estimates suggest that MMLs induce a $58 to $115 per-person annual reduction in obesity-related medical costs.”

http://www.ncbi.nlm.nih.gov/pubmed/26602324

Anti-Obesity Effect of the CB2 Receptor Agonist JWH-015 in Diet-Induced Obese Mice.

Posted on November 21, 2015 by David

“The cannabinoid receptor 2 (CB2) is well known for its immune modulatory role. However, recent localisation of CB2 receptors in metabolically active tissue suggests that the CB2 receptor plays a significant role in energy homeostasis.

This study was designed to investigate the impact of chronic CB2 receptor stimulation on food intake, body weight and mood.

These results demonstrate a role for CB2 receptors in modulating energy homeostasis and obesity associated metabolic pathologies in the absence of any adverse impact on mood.”

http://www.ncbi.nlm.nih.gov/pubmed/26588700