Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
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
_version_ 1782434914080129024
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
work_keys_str_mv AT fuhrmeisterjessica fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT zotaannika fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT sijmonsmatjeerdp fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT seibertoksana fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT cıngırsahika fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT schmidtkathrin fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT vallonnicola fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT deguiaroldanm fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT niopekkatharina fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT berrieldiazmauricio fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT maidaadriano fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT bluhermatthias fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT okunjurgeng fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT herzigstephan fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth
AT roseadamj fastinginducedlivergadd45brestrainshepaticfattyaciduptakeandimprovesmetabolichealth