The Endocannabinoid System and Its Relevance for Nutrition

Abstract

Endocannabinoids bind to cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. The biological actions of these polyunsaturated lipids are controlled by key agents responsible for their synthesis, transport and degradation, which together form an endocannabinoid system (ECS). In the past few years, evidence has been accumulated for a role of the ECS in regulating food intake and energy balance, both centrally and peripherally. In addition, up-regulation of the ECS in the gastrointestinal tract has a potential impact on inflammatory bowel diseases. In this review, the main features of the ECS are summarized in order to put in better focus our current knowledge of the nutritional relevance of endocannabinoid signaling and of its role in obesity, cardiovascular pathologies, and gastrointestinal diseases. The central and peripheral pathways that underlie these effects are discussed, as well as the possible exploitation of ECS components as novel drug targets for therapeutic intervention in eating disorders.

Common and divergent functions of Beclin 1 and Beclin 2

“…Moreover, these genotypes were associated with increased basal levels of multiple GPCRs, including CB1R and dopamine receptor D2 (DRD2) [7]. In line with the notion that increased CB1R signaling accrues food intake and hence favors obesity and insulin resistance, while pharmacological or genetic CB1R inhibition has opposite effects [9], Becn2 +/− mice accumulated more weight than their wild-type littermates in response to a standard (as well as to a high-fat) diet. At odds with their Becn1 +/− counterparts, Becn2 +/− mice also exhibited impaired glucose tolerance and decreased insulin sensitivity, two effects that could be reverted by a chemical CB1R antagonist [7].…”

PUFA-derived endocannabinoids: an overview

“…Other studies have shown an increased formation of DHEA and EPEA in various tissues, including prostate and breast cancer cells, after administering fish oil or individual n-3 long-chain PUFA (19,20) . Interestingly, we have also reported evidence that both DHEA and EPEA show greater anti-proliferative effects than their parent compounds, DHA and EPA, in two prostate cancer cell lines, LNCaP and PC3 cells (15) .…”

“…All stimuli involved in feeding are centrally integrated by the hypothalamus, a brain area known to play an important role in homoeostatic control, thus maintaining an adequate body weight (19) . There is now convincing evidence that the endocannabinoid system is involved in the regulation of food intake and energy expenditure.…”

Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss

“…[1][2][3][4] As endocannabinoids (ECs) are produced on demand in specific tissues, 5 what is measured in the circulation is probably spillover of unknown origin. Previous studies indicate a dysregulation of the ECS in human obesity with differentially regulated levels in various AT depots.…”

“…14 The ECs function mainly as neurotransmitters, and because of their highly lipophilic nature, they cannot be stored in vesicles and have to be produced on demand. 5 2-AG is synthesised by diacylglycerol lipase and degraded by monoglyceride lipase (MGL), 15 whereas AEA can be produced by N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and degraded by fatty acid amide hydrolase (FAAH). 16 Several forms of this enzyme exist, both FAAH2 and N-acylethanolamine-hydrolysing acid amidase but their roles are less characterised.…”