Endocannabinoids in appetite control and the treatment of obesity
Kirkham TC, Tucci SA (2006) CNS Neurol Disord Drug Targets. 2006 Jun;5(3): 272-92
Abstract:
Research into the endocannabinoid 'system' has grown exponentially in recent years, with the discovery of cannabinoid receptors and their endogenous ligands, such as anandamide and 2-arachidonoylglycerol (2-AG).Important advances have been made in our understanding of endocannabinoid transduction mechanisms, their metabolic pathways, and of the biological processes in which they are implicated. A decade of endocannabinoid studies has promoted new insights into neural regulation and mammalian physiology that are as revolutionary as those arising from the discovery of the endogenous opioid peptides in the 1970s.
Thus, endocannabinoids have been found to act as retrograde signals: released by postsynaptic neurons, they bind to presynaptic heteroceptors to modulate the release of inhibitory and excitatory neurotransmitters through multiple G-protein-coupled receptor (GPCR)-linked effector mechanisms. The metabolic pathways of anandamide and 2-AG have now been been characterised in great detail, and we can anticipate that these pathways - together with endocannabinoid uptake mechanisms - will complement cannabinoid receptors as targets for the pharmacological analysis of the physiological functions of these substances.
Specific insights into the potential role of endocannabinoid-CB1 receptor systems in central appetite control, peripheral metabolism and body weight regulation herald the clinical application of CB1 receptor antagonists in the management of obesity and its associated disorders.
FAB RESEARCH COMMENT:
The endocannabinoids are hormone-like substances made within the body, which activate the same receptors as the active substances in cannabis or marijuana - hence their name.Since their discovery in the 1990s, research has shown that endocannabinoid signalling is involved in a huge range of brain and body functions - including pain, appetite, temperature regulation, sleep, movement, perception and cognition.
Importantly, the main endocannabinoids are derived from the omega-6 and omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) - which must be derived from diet (or synthesised from shorter chain versions, although this process is highly inefficient).
The balance of these essential fats in modern, western-type diets has changed dramatically from the diet on which humans evolved. Specifically, modern, western-type diets contain far more omega-6 fats (from vegetable oils, and meat & dairy) and are seriously lacking in long-chain omega-3 (from fish and seafood).
This high ratio of omega-6 to omega-3 fats affects the balance of numerous substances derived from these key fatty acids - and has long been known to promote both excessive inflammation and blood clotting, via other derivatives of omega-3 and omega-6 LC-PUFA - and therefore to contribute to many of the 'non-communicable diseases' that now make up most of the burden of ill health.
As the main cannabionoid receptor (CB1) is the most common receptor in the human brain, it seems more than likely that imbalances of endocannabinoids, resulting from this omega-6/3 imbalance, will be found to play a part in mental health conditions, as well as appetite and obesity.
And although the authors make reference to potential pharmaceutical applications of research into the endocannabinoids, it seems likely that dietary changes could have equally important (and possibly safer) applications.
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