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Series GSE29984 Query DataSets for GSE29984
Status Public on Aug 04, 2011
Title Deletion of the Mammalian INDY Homologue in Mice Mimics Aspects of Dietary Restriction and Protects Against Diet and Age-Induced Adiposity and Insulin Resistance
Organism Mus musculus
Experiment type Expression profiling by array
Summary Reduction in expression of the INDY gene in Drosophila melanogaster and Caenorhabditis 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. In order to examine the effect that INDY might have on energy metabolism and insulin sensitivity in mammals we created the first knock out mouse model of the mammalian INDY homologue SLC13A5. Here, we show that deletion of the mammalian homologue of INDY, SLC13A5 (mINDY) in mice (mINDY-/- mice) have increased mitochondrial biogenesis, hepatic lipid oxidation, and energy expenditure, but decreased hepatic de novo lipogenesis. Loss of mIndy activates hepatic AMPK, which induces PGC-1?, inhibits ACC-2, and reduces SREBP-1c levels. In contrast to wild- type mice, mINDY-/- mice have reduced body weight and are protected from insulin resistance that evolves with high-fat feeding and aging. These studies demonstrate that mIndy functions as a novel regulator of mammalian energy metabolism and suggest that mIndy might be a novel therapeutic target for the treatment of obesity and type 2 diabetes.
 
Overall design An SLC13A5 knockout mouse model (mINDY-/-) was generated. The litters produced when heterozygous (KO/+) mINDY mice (mINDY+/-) were bred, contained the expected ratio of Illumina Mouse-ref8Indy wild-type (mINDY+/+), mINDY+/- mice, and homozygous mIndy (mINDY-/-) pups, indicating no substantial embryonic lethality. In wild-type mice, Indy mRNA expression was highest in liver, and very low in white adipose tissue, brown adipose tissue, skeletal muscle, small and large intestines and the pancreas confirming previous mINDY expression levels in rodents, and humans. In the liver, mINDY mRNA expression was completely abolished in the INDY-/- mice and ~50% reduced in heterozygous mINDY+/- mice. Total RNA from the Liver tissue of 5 replicate Wt and 5 replicate Knockout mice were labeled and hybridized to Illumina Mouse-ref8 v2 bead arrays. Analysis of gene expression was carried out by Hierarchy clustering/K-means clustering and Principal Components Analysis (PCA), as well as The Parameterized Analysis of Gene Enrichment (PAGE) and Ingenuity Pathways Analysis IPA (Ingenuity Systems, CA, USA).
 
Contributor(s) Birkenfeld AL, Lee H, Guebre-Egziabher F, Jurczak MJ, Jornayvaz FR, Alves T, Zhang D, Hsiao JJ, Martin-Montalvo A, Fischer-Rosinsky A, Spranger J, Willmitzer L, Pfeiffe AF, Carmean CM, Weismann D, Knauf F, Irusta PM, De Cabo R, Helfand SL, Samue VT, Shulman GI
Citation(s) 21803289
Submission date Jun 15, 2011
Last update date Jun 22, 2020
Contact name Supriyo De
Organization name NIA-IRP, NIH
Department Laboratory of Genetics and Genomics
Lab Computational Biology & Genomics Core
Street address 251 Bayview Blvd
City Baltimore
State/province Maryland
ZIP/Postal code 21224
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (10)
GSM742090 YI-KO-10
GSM742091 YI-KO-2
GSM742092 YI-KO-4
Relations
BioProject PRJNA140701

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE29984_RAW.tar 3.1 Mb (http)(custom) TAR
GSE29984_non-normalized.txt.gz 4.9 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table
Raw data included within Sample table

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