Metabolic and inflammatory functions of cannabinoid receptor type 1 are differentially modulated by adiponectin. Journal Article


Authors: Wei, Q; Lee, JH; Wu, CS; Zang, QS; Guo, S; Lu, HC; Sun, Y
Article Title: Metabolic and inflammatory functions of cannabinoid receptor type 1 are differentially modulated by adiponectin.
Abstract: BACKGROUND: Antagonists of cannabinoid type 1 receptor () have been shown to promote body weight loss and improve insulin sensitivity. Cannabinoids decrease adiponectin, and blocker increase adiponectin. However, the mediators of actions are not well defined. AIM: To investigate whether the beneficial effects of inhibition are, at least in part, mediated by adiponectin. METHODS: We compared metabolic and inflammatory phenotypes of wild-type (WT) mice, -null ( ) and /adiponectin double-knockout (DKO) mice. We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test, and inflammation using flow cytometry analysis of macrophages. RESULTS: mice exhibited significantly reduced body weight and fat mass when compared to WT mice. While no significance was found in total daily food intake and locomotor activity, mice showed increased energy expenditure, enhanced thermogenesis in brown adipose tissue (BAT), and improved insulin sensitivity compared to WT mice. DKO showed no difference in body weight, adiposity, nor insulin sensitivity; only showed a modestly elevated thermogenesis in BAT compared to mice. The metabolic phenotype of DKO is largely similar to mice, suggesting that adiponectin is not a key mediator of the metabolic effects of . Interestingly, mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice; in contrast, DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to mice, suggesting that adiponectin is an important mediator of the inflammatory effect of . CONCLUSION: Our findings reveal that functions through both adiponectin-dependent and adiponectin-independent mechanisms: regulates energy metabolism in an adiponectin-independent manner, and inflammation in an adiponectin-dependent manner. The differential effects of adiponectin on -mediated metabolic and inflammatory functions should be taken into consideration in antagonist utilization.
Journal Title: World journal of diabetes
Publisher: Unknown  
Date Published: 2021