title: Chronic AMP-kinase activation with AICAR reduces adiposity by remodeling adipocyte metabolism and increasing leptin sensitivity.
abstract: 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 the implications for visceral (VC) and subcutaneous (SC) adiposity, whole body-energy homeostasis, and hypothalamic leptin sensitivity. Male Wistar rats received daily single intraperitoneal injections of either saline or AICAR (0.7g/kg body weight) for 4 and 8 weeks and were pair-fed throughout the study. AICAR-treated rats had reduced adiposity with increased mitochondrial density in VC and SC fat pads, which was accompanied by reduced circulating leptin and time-dependent and depot-specific regulation of AMPK phosphorylation and FA oxidation. Interestingly, the anorectic effect to exogenous leptin was more pronounced in AICAR-treated animals than controls. This corresponded to reductions in hypothalamic AMPK phosphorylation and suppressor of cytokine signaling 3 content, whereas signal transducer and activator of transcription 3 phosphorylation was either unchanged or increased at 4 and 8 weeks in AICAR-treated rats. Ambulatory activity and whole-body energy expenditure (EE) were also increased with AICAR treatment. Altogether, chronic AICAR-induced AMPK activation increased WAT oxidative machinery, whole-body EE, and hypothalamic leptin sensitivity. This led to significant reductions in VC and SC adiposity without inducing energy-sparing mechanisms that oppose long-term fat loss.
authors: Muscle Health Research Centre-School of Kinesiology and Health Science, York University, Toronto, ON, Canada.
authors: Mandeep P
authors: MP
authors: Gaidhu
authors: Andrea
authors: A
authors: Frontini
authors: Steven
authors: S
authors: Hung
authors: Kathryn
authors: K
authors: Pistor
authors: Saverio
authors: S
authors: Cinti
authors: Rolando B
authors: RB
authors: Ceddia
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D020738:Leptin; D010168:Palmitates; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000263:Adenylate Kinase; C031143:AICA ribonucleotide