Cannabinoid Receptor Signaling Directly Inhibits Thermogenesis and Alters Expression of Adiponectin and Visfatin

Introduction

The endocannabinoid system has recently emerged as a critical component in the control of energy homeostasis. It is considered to be a general stress-recovery system and stimulates food intake [1]. Cannabinoid type 1 (Cb1) receptor-deficient mice are leaner than their wild-type littermates [2]. Furthermore, these animals are protected against diet-induced obesity [3]. The selective Cb1 receptor blocker Rimonabant promotes weight loss in large clinical trials in obese and insulin-resistant individuals [4] [5]. Both central and peripheral actions of the endocannabinoid system contribute to the regulation food intake and energy expenditure [6]. The Cb1 receptor is expressed in adipocytes [7]. However, little is known to date about direct Cb1 receptor-mediated actions on important functional levels of adipose tissue implicated in the control of energy and glucose homeostasis. Here, we present the first evidence for direct Cb1 receptor-mediated actions in brown and white adipocytes. Cannabinoid signaling negatively impacts thermogenesis in brown adipocytes while favoring a positive energy balance by differentially regulating the novel adipokine visfatin as well as adiponectin in white adipocytes.

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