A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome

• DOI: 10.1073/pnas.1421420112
• Publication Date: 2014-12-23T03:44:11Z
• Authors: Nicole P. Bowles; Ilia N. Karatsoreos; Xiaosong Li; V. Kiran Vemuri; Jodi-Anne Wood; Zhiying Li; Kellie L. K. Tama...; Gary J. Schwartz; Alexandros M. Mak...; George Kunos; Cecilia J. Hillard; Bruce S. McEwen; Matthew N. Hill
• Keywords: Metabolic Syndrome; 2. Zero hunger; 0303 health sciences; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; Liver; Receptor, Cannabinoid, CB1; Organ Specificity; Animals; Obesity; RNA, Messenger; Corticosterone; Glucocorticoids; Dyslipidemias; Endocannabinoids; Signal Transduction

Significance Obesity and associated metabolic disorders (e.g., cardiovascular disease and type 2 diabetes) are major public health concerns. These disorders result, in part, from hormonal dysregulation, particularly of glucocorticoids (GCs; central regulators of metabolism and adipogenesis). The specific mechanisms by which GCs modulate these processes remain largely unknown, but GCs increase production of endocannabinoids—potent central and peripheral regulators of appetite, energy balance, and metabolism. Our results show that sustained exposure to GCs produces obesity and metabolic syndrome through a peripheral endocannabinoid mechanism. These data further our understanding of the role of endocannabinoid signaling to promote not only diet-induced, but also, hormonal-mediated obesity and support the argument that peripheral blockade of endocannabinoid signaling could be a potential treatment for obese conditions.