AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis
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 S...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/32656 |
| _version_ | 1828376064621019136 |
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| author | Sandra Galic Kim Loh Lisa Murray-Segal Gregory R Steinberg Zane B Andrews Bruce E Kemp |
| author_facet | Sandra Galic Kim Loh Lisa Murray-Segal Gregory R Steinberg Zane B Andrews Bruce E Kemp |
| author_sort | Sandra Galic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:55:03Z |
| format | Article |
| id | doaj.art-be3ecd99d63b4dea816561fddf4da4f8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:55:03Z |
| publishDate | 2018-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-be3ecd99d63b4dea816561fddf4da4f82022-12-22T02:05:05ZengeLife Sciences Publications LtdeLife2050-084X2018-02-01710.7554/eLife.32656AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesisSandra Galic0https://orcid.org/0000-0002-7611-5619Kim Loh1Lisa Murray-Segal2Gregory R Steinberg3Zane B Andrews4https://orcid.org/0000-0002-9097-7944Bruce E Kemp5https://orcid.org/0000-0001-6735-5082Department of Medicine, University of Melbourne, Fitzroy, Australia; St. Vincent’s Institute of Medical Research, Melbourne, AustraliaDepartment of Medicine, University of Melbourne, Fitzroy, Australia; St. Vincent’s Institute of Medical Research, Melbourne, AustraliaDepartment of Medicine, University of Melbourne, Fitzroy, Australia; St. Vincent’s Institute of Medical Research, Melbourne, AustraliaDivision of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, CanadaBiomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia; Department of Physiology, Monash University, Clayton, Australia; Monash Biomedicine Discovery Institute, Monash University, Clayton, AustraliaDepartment of Medicine, University of Melbourne, Fitzroy, Australia; St. Vincent’s Institute of Medical Research, Melbourne, Australia; Mary MacKillop Institute for Health Research, Australian Catholic University, Fitzroy, AustraliaAMP-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.https://elifesciences.org/articles/32656AppetitecoldAMPKacetyl-CoA carboxylasefastingthermogenesis |
| spellingShingle | Sandra Galic Kim Loh Lisa Murray-Segal Gregory R Steinberg Zane B Andrews Bruce E Kemp AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis eLife Appetite cold AMPK acetyl-CoA carboxylase fasting thermogenesis |
| title | AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis |
| title_full | AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis |
| title_fullStr | AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis |
| title_full_unstemmed | AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis |
| title_short | AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis |
| title_sort | ampk signaling to acetyl coa carboxylase is required for fasting and cold induced appetite but not thermogenesis |
| topic | Appetite cold AMPK acetyl-CoA carboxylase fasting thermogenesis |
| url | https://elifesciences.org/articles/32656 |
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