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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-?-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.

SUBMITTER: Gaidhu MP

PROVIDER: S-EPMC3151690 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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

Gaidhu Mandeep P MP Frontini Andrea A Hung Steven S Pistor Kathryn K Cinti Saverio S Ceddia Rolando B RB

Journal of lipid research 20110707 9

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-t ...[more]

PMID: 21737753

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Dataset Information

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

Publications

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

Similar Datasets

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