Chronic AMP-kinase activation with AICAR reduces adiposity by remodeling adipocyte metabolism and increasing leptin sensitivity

• DOI: 10.1194/jlr.m015354
• Publication Date: 2011-07-08T15:09:53Z
• Authors: Mandeep P. Gaidhu; Andrea Frontini; Steven Hung; Kathryn Pistor; Saverio Cinti; Rolando B. Ceddia
• Keywords: AMP-Activated Protein Kinase; Energy homeostasis; Resistin

This study investigated the effect of chronic AMP-kinase (AMPK) activation with 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) on white adipose tissue (WAT) metabolism and implications for visceral (VC) subcutaneous (SC) adiposity, whole body-energy homeostasis, hypothalamic leptin sensitivity. Male Wistar rats received daily single intraperitoneal injections either saline or AICAR (0.7g/kg body weight) 4 8 weeks were pair-fed throughout study. AICAR-treated had reduced adiposity increased mitochondrial density in VC SC fat pads, which was accompanied by circulating time-dependent depot-specific regulation AMPK phosphorylation FA oxidation. Interestingly, anorectic to exogenous more pronounced animals than controls. corresponded reductions suppressor cytokine signaling 3 content, whereas signal transducer activator transcription unchanged at rats. Ambulatory activity whole-body energy expenditure (EE) also treatment. Altogether, AICAR-induced WAT oxidative machinery, EE, led significant without inducing energy-sparing mechanisms that oppose long-term loss.