CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus.

Journal article

AMP-activated protein kinase (AMPK), a regulator of cellular and systemic energy homeostasis, can be influenced by several hormones. Tissue-specific alteration of AMPK activity by glucocorticoids may explain the increase in appetite, the accumulation of lipids in adipose tissues, and the detrimental cardiac effects of Cushing's syndrome. Endocannabinoids are known to mediate the effects of various hormones and to influence AMPK activity. Cannabinoids have central orexigenic and direct peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). In our preliminary experiments, WT mice received implants of a corticosterone-containing pellet to establish a mouse model of Cushing's syndrome. Subsequently, WT and Cb1 (Cnr1)-knockout (CB1-KO) littermates were treated with corticosterone and AMPK activity in the hypothalamus, various adipose tissues, liver and cardiac tissue was measured. Corticosterone-treated CB1-KO mice showed a lack of weight gain and of increase in hypothalamic and hepatic AMPK activity. In adipose tissues, baseline AMPK activity was higher in CB1-KO mice, but a glucocorticoid-induced drop was observed, similar to that observed in WT mice. Cardiac AMPK levels were reduced in CB1-KO mice, but while WT mice showed significantly reduced AMPK activity following glucocorticoid treatment, CB1-KO mice showed a paradoxical increase. Our findings indicate the importance of the CB1 receptor in the central orexigenic effect of glucocorticoid-induced activation of hypothalamic AMPK activity. In the periphery adipose tissues, changes may occur independently of the CB1 receptor, but the receptor appears to alter the responsiveness of the liver and myocardial tissues to glucocorticoids. In conclusion, our data suggest that an intact cannabinoid pathway is required for the full metabolic effects of chronic glucocorticoid excess.

Authors: Scerif, M; Füzesi, T; Thomas, J; Kola, B; Grossman, AB

• Publication status: Published
• Journal: Journal of endocrinology
• Volume: 219
• Issue: 1
• Pages: 79-88
• Publication date: 2013-10-01
• DOI: 10.1530/joe-13-0192
• EISSN: 1479-6805
• ISSN: 0022-0795
• Language: English
• Keywords: Liver; Male; Corticosterone; Hypothalamus; Myocardium; Adipose Tissue; Receptor, Cannabinoid, CB1; Glucocorticoids; AMP-Activated Protein Kinases; Disease Models, Animal; Cushing Syndrome; Mice; Animals