Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice.

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ID Serval
serval:BIB_21BAB299A947
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Production externe
Titre
Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice.
Périodique
Cell Metabolism
Auteur⸱e⸱s
Birkenfeld A.L., Lee H.Y., Guebre-Egziabher F., Alves T.C., Jurczak M.J., Jornayvaz F.R., Zhang D., Hsiao J.J., Martin-Montalvo A., Fischer-Rosinsky A., Spranger J., Pfeiffer A.F., Jordan J., Fromm M.F., König J., Lieske S., Carmean C.M., Frederick D.W., Weismann D., Knauf F., Irusta P.M., De Cabo R., Helfand S.L., Samuel V.T., Shulman G.I.
ISSN
1932-7420 (Electronic)
ISSN-L
1550-4131
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
14
Numéro
2
Pages
184-195
Langue
anglais
Résumé
Reduced expression of the Indy (I'm Not Dead, Yet) gene in D. melanogaster and its homolog in C. elegans prolongs life span and in D. melanogaster augments mitochondrial biogenesis in a manner akin to caloric restriction. However, the cellular mechanism by which Indy does this is unknown. Here, we report on the knockout mouse model of the mammalian Indy (mIndy) homolog, SLC13A5. Deletion of mIndy in mice (mINDY(-/-) mice) reduces hepatocellular ATP/ADP ratio, activates hepatic AMPK, induces PGC-1α, inhibits ACC-2, and reduces SREBP-1c levels. This signaling network promotes hepatic mitochondrial biogenesis, lipid oxidation, and energy expenditure and attenuates hepatic de novo lipogenesis. Together, these traits protect mINDY(-/-) mice from the adiposity and insulin resistance that evolve with high-fat feeding and aging. Our studies demonstrate a profound effect of mIndy on mammalian energy metabolism and suggest that mINDY might be a therapeutic target for the treatment of obesity and type 2 diabetes.
Mots-clé
Adiposity/genetics, Aging, Animals, Caloric Restriction, Dicarboxylic Acid Transporters, Energy Metabolism/genetics, HEK293 Cells, Humans, Insulin Resistance/genetics, Lipid Metabolism/genetics, Mice, Mice, Knockout, Mitochondria/genetics, Mitochondria/metabolism, Obesity/genetics, Symporters/biosynthesis, Symporters/deficiency
DOI
10.1016/j.cmet.2011.06.009
Pubmed
21803289
Web of science
000293606300009
Open Access
Oui
Création de la notice
10/09/2015 13:28
Dernière modification de la notice
20/08/2019 13:58
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