Endocannabinoid system in cancer cachexia.
OBJECTIVE
More than 60% of advanced cancer patients suffer from anorexia and cachexia. This review focuses on the possible mechanisms by which the endocannabinoid system antagonizes cachexia-anorexia processes in cancer patients and how it can be tapped for therapeutic applications.


RESULTS
Cannabinoids stimulate appetite and food intake. Hepatocytes express functional cannabinoid type 1 receptors, activation of which increases the expression of lipogenic genes (e.g those encoding sterol regulatory element binding protein 1c, acetyl-coenzyme A carboxylase-1, and fatty acid synthase in the liver and hypothalamus) and increase de-novo fatty acid synthesis, which contributes to development of diet-induced obesity. Both ghrelin and cannabinoids stimulate AMP-activated protein kinase in the hypothalamus, whereas they inhibit it in the liver and adipose tissues. Both anandamide and synthetic cannabinoid type 1 receptor agonists such as HU210 and the plant-derived cannabinoid tetrahydro-cannabinol also significantly inhibit tumor necrosis factor-alpha.


CONCLUSIONS
Cannabinoid type 1 receptor activation stimulates appetite and promotes lipogenesis and energy storage. Further study of cancer-cachexia pathophysiology and the role of endocannabinoids will help us to develop cannabinoids without psychotropic properties, which will help cancer patients suffering from cachexia and improve outcomes of clinical antitumor therapy.
Osei-Hyiaman
Douglas
D
Section on NeuroEndocrinology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-9413, USA. dhyiaman@gmail.com
D000855:Anorexia / Q000188:drug therapy / Q000503:physiopathology*; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D002100:Cachexia / Q000188:drug therapy / Q000503:physiopathology*; D063385:Cannabinoid Receptor Modulators / Q000502:physiology* / Q000627:therapeutic use; D004435:Eating / Q000187:drug effects / Q000502:physiology; D063388:Endocannabinoids; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1