ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 25 OC4.4

CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus but not in adipose tissues

Miski Scerif1, Blerina Kola1, Csaba Fekete2, Ashley B Grossman1 & Márta Korbonits1

1Department of Endocrinology, Barts and the London Medical School, William Harvey Research Institute, Queen Mary University of London, London, UK; 2Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.

Introduction: Adenosine monophosphate-activated protein kinase (AMPK) is a regulator of cellular and systemic energy homeostasis. Many of the changes seen in glucocorticoid excess correspond to the metabolic steps regulated by AMPK. In the hypothalamus and adipose tissues, glucocorticoids and cannabiniods share the same tissue specific effects on AMPK activity. Cannabinoids have central orexigenic and peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). The cannabiniod-CB1 system interacts with a number of hormonal systems and perhaps mediates their effects.

Aims: To investigate if the CB1 receptor is required for the tissue-specific effects of glucocorticoids on hypothalamic and adipose tissue AMPK activity.

Methods: Wild-type (WT) and CB1-KO mice were treated for 2 weeks with a surgically implanted pellet containing either cholesterol (control) or corticosterone (5 mg). Hypothalamic and adipose tissue AMPK activity was determined in a functional kinase assay by the entity of 32P incorporation into the synthetic AMPK substrate SAMS.

Results: Corticosterone significantly increased hypothalamic AMPK activity in WT mice (P=0.0007), but not in CB1-KO mice (P=0.636). WT mice treated with corticosterone, as compared to cholesterol treated controls, showed significantly decreased visceral (mesenteric) and subcutaneous (inguinal) fat AMPK activity (P<0.0001 for both). Corticosterone treated CB1-KO mice also showed significantly decreased visceral and subcutaneous fat AMPK activity as compared to cholesterol-treated controls (P=0.0017 and P=0.0013, respectively). However, CB1-KO mice showed higher baseline visceral (P=0.0125) and subcutaneous (P=0.0242) adipose tissue AMPK activity as compared to WT mice.

Conclusion: The stimulatory effects of glucocorticiods on hypothalamic AMPK activity are CB1-dependent. The CB1 receptor does not mediate the inhibitory effect of glucocorticoids on adipose tissue AMPK activity but has an independent inhibitory effect on adipose tissue AMPK activity.

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