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Title

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

Authors
Birkenfeld, Andreas L
Lee, Hui-Young
Guebre-Egziabher, Fitsum
Alves, Tiago C
Jurczak, Michael J
Zhang, Dongyang
Hsiao, Jennifer J
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Published in Cell Metabolism. 2011, vol. 14, no. 2, p. 184-95
Abstract 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.
Keywords Adiposity/geneticsAgingAnimalsCaloric RestrictionDicarboxylic Acid TransportersEnergy Metabolism/geneticsHEK293 CellsHumansInsulin Resistance/geneticsLipid Metabolism/geneticsMiceMiceKnockoutMitochondria/genetics/metabolismObesity/geneticsSymporters/biosynthesis/deficiency/genetics
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PMID: 21803289
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BIRKENFELD, Andreas L et al. Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice. In: Cell Metabolism, 2011, vol. 14, n° 2, p. 184-95. https://archive-ouverte.unige.ch/unige:100531

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Deposited on : 2017-12-19

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