Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #330486
Title: Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity

Author
item MEADOWS, ADELINA - Children'S Nutrition Research Center (CNRC)
item LEE, JONG HAN - Children'S Nutrition Research Center (CNRC)
item WU, CHIA-SHAN - Children'S Nutrition Research Center (CNRC)
item WEI, QIN - Children'S Nutrition Research Center (CNRC)
item PRADHAN, GEETALI - Children'S Nutrition Research Center (CNRC)
item YAFI, MICHAEL - University Of Texas
item LU, HUI-CHEN - Indiana University
item SUN, YUXIANG - Children'S Nutrition Research Center (CNRC)

Submitted to: International Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/21/2015
Publication Date: 3/15/2016
Citation: Meadows, A.G., Lee, J., Wu, C., Wei, Q., Pradhan, G., Yafi, M., Lu, H., Sun, Y. 2016. Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity. International Journal of Obesity. 40:417-424.

Interpretive Summary: G-protein-coupled receptor 55 (GPR55) is a newly identified cannabinoid receptor. The roles of GPR55 in energy and glucose homeostasis are unknown. We studied the functions of GPR55 in energy balance and insulin sensitivity using GPR55-null mice (GPR55-/-) where GPR55 is deleted in all tissues. We found that while adult GPR55-/- mice showed a modest increase in overall body weight, they exhibited significantly increased fat mass and insulin resistance. GPR55-/- mice exhibited significantly decreased voluntary physical activity, showing reduced running distance on the running wheels. Thus GPR55 has an important role in energy homeostasis. GPR55 ablation increases adiposity and insulin resistance by selectively decreasing physical activity.

Technical Abstract: Cannabinoid receptor 1 (CB1) is the best-characterized cannabinoid receptor, and CB1 antagonists are used in clinical trials to treat obesity. Because of the wide range of CB1 functions, the side effects of CB1 antagonists pose serious concerns. G-protein-coupled receptor 55 (GPR55) is an atypical cannabinoid receptor, and its pharmacology and functions are distinct from CB1. GPR55 regulates neuropathic pain, gut, bone, immune functions and motor coordination. GPR55 is expressed in various brain regions and peripheral tissues. However, the roles of GPR55 in energy and glucose homeostasis are unknown. Here we have investigated the roles of GPR55 in energy balance and insulin sensitivity using GPR55-null mice (GPR55(-/-)). Body composition of the mice was measured by EchoMRI. Food intake, feeding behavior, energy expenditure and physical activity of GPR55(-/-) mice were determined by indirect calorimetry. Muscle function was assessed by forced treadmill running test. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Adipose inflammation was assessed by flow cytometry analysis of adipose tissue macrophages. The expression of inflammatory markers in adipose tissues and orexigenic/anorexigenic peptides in the hypothalamus was also analyzed by real-time PCR. GPR55(-/-) mice had normal total energy intake and feeding pattern (i.e., no changes in meal size, meal number or feeding frequency). Intriguingly, whereas adult GPR55(-/-) mice only showed a modest increase in overall body weight, they exhibited significantly increased fat mass and insulin resistance. The spontaneous locomotor activity of GPR55(-/-) mice was dramatically decreased, whereas resting metabolic rate and non-shivering thermogenesis were unchanged. Moreover, GPR55(-/-) mice exhibited significantly decreased voluntary physical activity, showing reduced running distance on the running wheels, whereas muscle function appeared to be normal. GPR55 has an important role in energy homeostasis. GPR55 ablation increases adiposity and insulin resistance by selectively decreasing physical activity, but not by altering feeding behavior as CB1.