What Does Rimonabant Do in Rat Primary Skeletal Muscle Cells
Mansour Haddad

Department of Clinical Sciences, Faculty of Pharmacy, Philadelphia University, P.O box 3341, Irbid, Jordan P.C 211-10.

Abstract: Rimonabant decreases body weight in man and improves metabolic parameters in animal models of obesity. The contribution of peripheral targets, particularly skeletal muscle, for CB1 cannabinoid receptor antagonism in these effects is, however, unclear. The purpose of this study was, therefore, to investigate the impact of CB1 receptors inhibition upon downstream signalling and to characterize the molecular mechanisms that mediate the direct effects of rimonabant in rat primary skeletal muscle cells. Skeletal muscle cells were cultured from vastus lateralis obtained from 180-200 g male Wistar rats according to Blau and Webster method with slight modification. mRNA expression, and downstream signalling genes were examined by gene expression microarray. QRT-PCR (Taqman) identified CB1 cannabinoid receptor mRNA expression with Ct values of 26.5-27.5 in myoblasts, myotubes and skeletal muscle tissue. The findings from the present study indicate, for the first time, that rimonabant up-regulates the mRNA content of neuropeptide Y (NPY), apelin (APLN) and lipocalin 2 (LCN2), and down-regulate the mRNA content of G protein alpha subunit (GNAI3) and nuclear receptor subfamily 4, group A (NR4A). These findings provide evidence for potential functional role of rimonabant in skeletal muscle in terms of insulin resistance, glucose and fat metabolism, inflammation and myogenesis. The impact of CB1 receptor expression in skeletal muscle will be the subject of further investigation

Keywords: Rimonabant; skeletal muscle; myotube; signalling

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