Cannabinoid Type 1 Receptor Blockade Promotes Mitochondrial Biogenesis Through Endothelial Nitric Oxide Synthase Expression in White Adipocytes

• DOI: 10.2337/db07-1623
• Publication Date: 2008-05-14T01:49:42Z
• Authors: Laura Tedesco; Alessandra Valerio; Cristina Cervino; Annalisa Cardile; Claudio Pagano; Roberto Vettor; Renato Pasquali; Michele O. Carruba; Giovanni Marsicano; Beat Lutz; Uberto Pagotto; Enzo Nisoli
• Keywords: Male; 0301 basic medicine; Dose-Response Relationship, Drug; Nitric Oxide Synthase Type III; Adipocytes, White; Immunoblotting; Citrate (si)-Synthase; AMP-Activated Protein Kinases; Protein Serine-Threonine Kinases; Flow Cytometry; DNA, Mitochondrial; Mitochondria; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Metabolism; Adenosine Triphosphate; Piperidines; Multienzyme Complexes; Animals; Pyrazoles; Phosphorylation; Cells, Cultured

OBJECTIVE—Cannabinoid type 1 (CB1) receptor blockade decreases body weight and adiposity in obese subjects; however, the underlying mechanism is not yet fully understood. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) induces mitochondrial biogenesis function adipocytes. This study was undertaken to test whether CB1 increases espression of eNOS white RESEARCH DESIGN AND METHODS—We examined effects on selective pharmacological receptors SR141716 (rimonabant) mouse primary We also expression adipose tissue (WAT) isolated mature adipocytes receptor–deficient (CB1−/−) chronically SR141716-treated mice either a standard or high-fat diet. RESULTS—SR141716 treatment increased cultured Moreover, DNA amount, mRNA levels genes involved biogenesis, mass through induction, as demonstrated reversal small interfering RNA–mediated decrease eNOS. While diet–fed wild-type showed reduced WAT adipocytes, genetic deletion chronic with restored these parameters observed diet, an effect linked prevention increase. CONCLUSIONS—CB1 inducing diet–induced fat accumulation, without concomitant changes food intake.