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Publication
Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and
protects against adiposity and insulin resistance in mice.
Authors Birkenfeld AL, Lee HY, Guebre-Egziabher F, Alves TC, Jurczak MJ, Jornayvaz FR,
Zhang D, Hsiao JJ, Martin-Montalvo A, Fischer-Rosinsky A, Spranger J, Pfeiffer
AF, Jordan J, Fromm MF, König J, Lieske S, Carmean CM, Frederick DW, Weismann D,
Knauf F, Irusta PM, De Cabo R, Helfand SL, Samuel VT, Shulman GI
Submitted By Andreas Birkenfeld on 10/11/2012
Status Published
Journal Cell Metabolism
Year 2011
Date Published 8/3/2011
Volume : Pages 14 : 184 - 195
PubMed Reference 21803289
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-1a, 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.




Strains
StrainDevelopment StatusCreation MethodOptions
C57BL/6-Slc13a5tm1.2HelfPhenotyping ongoingrecombinant congenic
View




Genes
SymbolDescription
Slc13a5solute carrier family 13 (sodium-dependent citrate transporter), member 5

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