AMPK signaling to acetyl-CoA carboxylase is required for fasting - and cold-induced appetite but not thermogenesis
Journal article
Galic, Sandra, Loh, Kim, Murray-Segal, Lisa, Steinberg, Gregory R., Andrews, Zane B. and Kemp, Bruce. (2018). AMPK signaling to acetyl-CoA carboxylase is required for fasting - and cold-induced appetite but not thermogenesis. eLife. 7, pp. 1 - 22. https://doi.org/10.7554/eLife.32656
Authors | Galic, Sandra, Loh, Kim, Murray-Segal, Lisa, Steinberg, Gregory R., Andrews, Zane B. and Kemp, Bruce |
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Abstract | AMP-activated protein kinase (AMPK) is a known regulator of whole-body energy homeostasis, but the downstream AMPK substrates mediating these effects are not entirely clear. AMPK inhibits fatty acid synthesis and promotes fatty acid oxidation by phosphorylation of acetyl-CoA carboxylase (ACC) 1 at Ser79 and ACC2 at Ser212. Using mice with Ser79Ala/Ser212Ala knock-in mutations (ACC DKI) we find that inhibition of ACC phosphorylation leads to reduced appetite in response to fasting or cold exposure. At sub-thermoneutral temperatures, ACC DKI mice maintain normal energy expenditure and thermogenesis, but fail to increase appetite and lose weight. We demonstrate that the ACC DKI phenotype can be mimicked in wild type mice using a ghrelin receptor antagonist and that ACC DKI mice have impaired orexigenic responses to ghrelin, indicating ACC DKI mice have a ghrelin signaling defect. These data suggest that therapeutic strategies aimed at inhibiting ACC phosphorylation may suppress appetite following metabolic stress. |
Keywords | cetyl coenzyme A carboxylase; ghrelin; insulin; AMPK signaling; animal experiment; appetite; body mass; cold; controlled study; nuclear magnetic resonance spectroscopy; thermogenesis; immunohistochemistry |
Year | 2018 |
Journal | eLife |
Journal citation | 7, pp. 1 - 22 |
Publisher | eLife Sciences Publications Ltd |
ISSN | 2050-084X |
Digital Object Identifier (DOI) | https://doi.org/10.7554/eLife.32656 |
Scopus EID | 2-s2.0-85043529407 |
Open access | Open access |
Page range | 1 - 22 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | |
Place of publication | United Kingdom |
Editors | R. Schekman |
https://acuresearchbank.acu.edu.au/item/883vq/ampk-signaling-to-acetyl-coa-carboxylase-is-required-for-fasting-and-cold-induced-appetite-but-not-thermogenesis
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