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Fasting‐induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health
Recent studies have demonstrated that repeated short‐term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888855/ https://www.ncbi.nlm.nih.gov/pubmed/27137487 http://dx.doi.org/10.15252/emmm.201505801 |
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author | Fuhrmeister, Jessica Zota, Annika Sijmonsma, Tjeerd P Seibert, Oksana Cıngır, Şahika Schmidt, Kathrin Vallon, Nicola de Guia, Roldan M Niopek, Katharina Berriel Diaz, Mauricio Maida, Adriano Blüher, Matthias Okun, Jürgen G Herzig, Stephan Rose, Adam J |
author_facet | Fuhrmeister, Jessica Zota, Annika Sijmonsma, Tjeerd P Seibert, Oksana Cıngır, Şahika Schmidt, Kathrin Vallon, Nicola de Guia, Roldan M Niopek, Katharina Berriel Diaz, Mauricio Maida, Adriano Blüher, Matthias Okun, Jürgen G Herzig, Stephan Rose, Adam J |
author_sort | Fuhrmeister, Jessica |
collection | PubMed |
description | Recent studies have demonstrated that repeated short‐term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered “growth arrest and DNA damage‐inducible” GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre‐diabetes and type 2 diabetes, in both mice and humans. Using whole‐body knockout mice as well as liver/hepatocyte‐specific gain‐ and loss‐of‐function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity‐driven hyperglycaemia. In summary, fasting stress‐induced GADD45β represents a liver‐specific molecular event promoting adaptive metabolic function. |
format | Online Article Text |
id | pubmed-4888855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48888552016-12-12 Fasting‐induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health Fuhrmeister, Jessica Zota, Annika Sijmonsma, Tjeerd P Seibert, Oksana Cıngır, Şahika Schmidt, Kathrin Vallon, Nicola de Guia, Roldan M Niopek, Katharina Berriel Diaz, Mauricio Maida, Adriano Blüher, Matthias Okun, Jürgen G Herzig, Stephan Rose, Adam J EMBO Mol Med Research Articles Recent studies have demonstrated that repeated short‐term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered “growth arrest and DNA damage‐inducible” GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre‐diabetes and type 2 diabetes, in both mice and humans. Using whole‐body knockout mice as well as liver/hepatocyte‐specific gain‐ and loss‐of‐function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity‐driven hyperglycaemia. In summary, fasting stress‐induced GADD45β represents a liver‐specific molecular event promoting adaptive metabolic function. John Wiley and Sons Inc. 2016-05-03 2016-06 /pmc/articles/PMC4888855/ /pubmed/27137487 http://dx.doi.org/10.15252/emmm.201505801 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Fuhrmeister, Jessica Zota, Annika Sijmonsma, Tjeerd P Seibert, Oksana Cıngır, Şahika Schmidt, Kathrin Vallon, Nicola de Guia, Roldan M Niopek, Katharina Berriel Diaz, Mauricio Maida, Adriano Blüher, Matthias Okun, Jürgen G Herzig, Stephan Rose, Adam J Fasting‐induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health |
title | Fasting‐induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health |
title_full | Fasting‐induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health |
title_fullStr | Fasting‐induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health |
title_full_unstemmed | Fasting‐induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health |
title_short | Fasting‐induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health |
title_sort | fasting‐induced liver gadd45β restrains hepatic fatty acid uptake and improves metabolic health |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888855/ https://www.ncbi.nlm.nih.gov/pubmed/27137487 http://dx.doi.org/10.15252/emmm.201505801 |
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