The Endocannabinoid System: Pivotal Orchestrator of Obesity and Metabolic Disease.

Posted on September 29, 2015 by David

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“The endocannabinoid system (ECS) functions to adjust behavior and metabolism according to environmental changes in food availability.

Its actions range from the regulation of sensory responses to the development of preference for the consumption of calorically-rich food and control of its metabolic handling.

ECS activity is beneficial when access to food is scarce or unpredictable.

However, when food is plentiful, the ECS favors obesity and metabolic disease.

We review recent advances in understanding the roles of the ECS in energy balance, and discuss newly identified mechanisms of action that, after the withdrawal of first generation cannabinoid type 1 (CB1) receptor antagonists for the treatment of obesity, have made the ECS once again an attractive target for therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/26412154

https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(15)00140-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS104327601500140X%3Fshowall%3Dtrue

Endocannabinoids and Metabolic Disorders.

Posted on September 27, 2015 by David

“The endocannabinoid system (ECS) is known to exert regulatory control on essentially every aspect related to the search for, and the intake, metabolism and storage of calories, and consequently it represents a potential pharmacotherapeutic target for obesity, diabetes and eating disorders.

While the clinical use of the first generation of cannabinoid type 1 (CB1) receptor blockers has been halted due to the psychiatric side effects that their use occasioned, recent research in animals and humans has provided new knowledge on the mechanisms of actions of the ECS in the regulation of eating behavior, energy balance, and metabolism.

In this review, we discuss these recent advances and how they may allow targeting the ECS in a more specific and selective manner for the future development of therapies against obesity, metabolic syndrome, and eating disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26408168

New insights on the role of the endocannabinoid system in the regulation of energy balance.

Posted on September 17, 2015 by David

“Within the last 15 years, the endocannabinoid system (ECS) has emerged as a lipid signaling system critically involved in the regulation of energy balance, since it exerts a regulatory control on every aspect related to the search, the intake, the metabolism and the storage of calories.

An overactive endocannabinoid-cannabinoid type 1 (CB1) receptor signaling promotes the development of obesity, insulin resistance and dyslipidemia, representing a valuable pharmacotherapeutic target for obesity and metabolic disorders.

However, due to psychiatric side effects, the first generation of brain-penetrant CB1 receptor blockers developed as anti-obesity treatment was removed from the European market in late 2008.

Since then, recent studies have identified new mechanisms of action of the ECS in energy balance and metabolism, as well as novel ways of targeting the system that may be efficacious for the treatment of obesity and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26374449

G protein-coupled receptor 18: A potential role for endocannabinoid signalling in metabolic dysfunction.

Posted on September 5, 2015 by David

“Endocannabinoids are products of dietary fatty acids that are modulated by an alteration in food intake levels.

Overweight and obese individuals have substantially higher circulating levels of the arachidonic acid-derived endocannabinoids, anandamide and 2-arachidonoyl glycerol, and show an altered pattern of cannabinoid receptor expression.

These cannabinoid receptors are part of a large family of G protein-coupled receptors (GPCRs).

GPCRs are major therapeutic targets for various diseases within the cardiovascular, neurological, gastrointestinal and endocrine systems, as well as metabolic disorders such as obesity and type 2 diabetes mellitus.

Obesity is considered a state of chronic low grade inflammation elicited by an immunological response.

Interestingly, the newly deorphanised G protein-coupled receptor GPR18, which is considered to be a putative cannabinoid receptor, is proposed to have an immunological function.

In this review, the current scientific knowledge on GPR18 is explored including its localisation, signalling pathways and pharmacology.

Importantly, the involvement of nutritional factors and potential dietary regulation of GPR18 and its (patho)physiological roles are described.

Further research on this receptor and its regulation will enable a better understanding of the complex mechanisms of GPR18 and its potential as a novel therapeutic target for treating metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26337420

Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its antinociceptive effect.

Posted on July 25, 2015 by David

“Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes.

It is well known that diabetic animals are less sensitive to the analgesic effect of morphine, and opioids are found to be ineffective in the treatment of diabetic neuropathic pain.

Cannabinoids are promising drugs and they share a similar pharmacological properties with opioids.

It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury.

Thus, we investigated antinociceptive efficacy and the effects of cannabinoids on behavioral sign of diabetic neuropathic pain in diabetic mice by using WIN 55, 212-2, a cannabinoid receptor agonist.

This study suggests that cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/15342139

Hydroxytyrosol Inhibits Cannabinoid CB1 Receptor Gene Expression in 3T3-L1 Preadipocyte Cell Line.

Posted on July 22, 2015 by David

“The 3T3-L1 preadipocyte cell line is a well characterized cell model for studying the adipocyte status and the molecular mechanisms involved in differentiation of these cells. 3T3-L1 preadipocytes have the ability to synthesize and degrade endocannabinoid anandamide (AEA) and their differentiation into adipocytes increases the expression of cannabinoid (CB1) and PPAR-γ receptors.

Clinically, the blocking stimulation of the endocannabinoid pathway has been one of the first approaches proposed to counteract the obesity and obesity-associated diseases (such as diabetes, metabolic syndrome and cancer).

In this connection, here we studied in cultured 3T3-L1 pre-adipocytes the effects of n-3-PUFA, α-Linolenic acid (OM-3), n-6-PUFA, Linoleic acid (OM-6) and hydroxytyrosol (HT) on the expression of CB1 receptor gene and the adipogenesis-related genes PPAR-γ, Fatty Acid Synthase (FAS) and Lipoprotein Lipase (LPL).

HT was able to inhibit 3T3-L1 cell differentiation by down-regulating cell proliferation and CB1 receptor gene expression. HT exhibited anti-adipogenic effects, whereas OM-3 and OM-6 exerted an inhibitory action on cell proliferation associated with an induction of the preadipocytes differentiation and CB1 receptor gene expression.

Moreover, the expression of FAS and LPL genes resulted increased after treatment with both HT and OM-3 and OM-6.

The present study points out that the intake of molecules such as HT, contained in extra virgin olive oil, may be considered also in view of antiobesity and antineoplastic properties by acting directly on the adipose tissue and modulating CB1 receptor gene transcription.”

http://www.ncbi.nlm.nih.gov/pubmed/26189725

Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH).

Posted on June 17, 2015 by David

“Diabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients…

Cannabis has been associated with reduced IR risk in some population-based surveys.

We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients…

Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients.

The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice.”

http://www.ncbi.nlm.nih.gov/pubmed/25778750

Brief Report: Cannabis Smoking and Diabetes Mellitus: Results from Meta-analysis with Eight Independent Replication Samples.

Posted on June 17, 2015 by David

“Recently active cannabis smoking and diabetes mellitus are inversely associated…

…but there now is a more stable evidence base for new lines of clinical translational research on a possibly protective cannabis smoking-diabetes mellitus association suggested in prior research.”

http://www.ncbi.nlm.nih.gov/pubmed/25978795

http://www.thctotalhealthcare.com/category/diabetes/

Role of the Endocannabinoid System in Diabetes and Diabetic Complications.

Posted on June 17, 2015 by David

“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, and by exerting pro-apoptotic effects in pancreatic β cells, and by facilitating inflammation in pancreatic islets.

Furthermore, hyperglycemia associated with diabetes has also been implicated in triggering perturbations of the ECS amplifying the above mentioned pathological processes, 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.”

http://www.ncbi.nlm.nih.gov/pubmed/26076890#

http://www.thctotalhealthcare.com/category/diabetes/

Neuroprotective effects of cannabidiol in endotoxin-induced uveitis: critical role of p38 MAPK activation.

Posted on May 16, 2015 by David

“Degenerative retinal diseases are characterized by inflammation and microglial activation.

The nonpsychoactive cannabinoid, cannabidiol (CBD), is an anti-inflammatory in models of diabetes and glaucoma.

We tested the hypothesis that retinal inflammation and microglia activation are initiated and sustained by oxidative stress and p38 mitogen-activated protein kinase (MAPK) activation, and that CBD reduces inflammation by blocking these processes…

Retinal inflammation and degeneration in uveitis are caused by oxidative stress.

CBD exerts anti-inflammatory and neuroprotective effects by a mechanism that involves blocking oxidative stress and activation of p38 MAPK and microglia.”

http://www.ncbi.nlm.nih.gov/pubmed/19052649