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J Biol Chem. 2014 Oct 17;289(42):29112-22. doi: 10.1074/jbc.M114.571679. Epub 2014 Sep 4.

Up-regulation of the Sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) genes in white adipose tissue of Id1 protein-deficient mice: implications in the protection against diet and age-induced glucose intolerance.

Author information

1
From the Program in Immunobiology and Cancer Research.
2
From the Program in Immunobiology and Cancer Research, Department of Cell Biology and.
3
Program in Free Radical Biology and Aging, and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, and.
4
Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104.
5
Department of Physiology and Biophysics, Rutgers University, Piscataway, New Jersey 08854.
6
From the Program in Immunobiology and Cancer Research, Department of Cell Biology and sunx@omrf.org.

Abstract

Id1, a helix-loop-helix (HLH) protein that inhibits the function of basic HLH E protein transcription factors in lymphoid cells, has been implicated in diet- and age-induced obesity by unknown mechanisms. Here we show that Id1-deficient mice are resistant to a high fat diet- and age-induced obesity, as revealed by reduced weight gain and body fat, increased lipid oxidation, attenuated hepatosteatosis, lower levels of lipid droplets in brown adipose tissue, and smaller white adipocytes after a high fat diet feeding or in aged animals. Id1 deficiency improves glucose tolerance, lowers serum insulin levels, and reduces TNFα gene expression in white adipose tissue. Id1 deficiency also increased expression of Sirtuin 1 and peroxisome proliferator-activated receptor γ coactivator 1α, regulators of mitochondrial biogenesis and energy expenditure, in the white adipose tissue. This effect was accompanied by the elevation of several genes encoding proteins involved in oxidative phosphorylation and fatty acid oxidation, such as cytochrome c, medium-chain acyl-CoA dehydrogenase, and adipocyte protein 2. Moreover, the phenotype for Id1 deficiency was similar to that of mice expressing an E protein dominant-positive construct, ET2, suggesting that the balance between Id and E proteins plays a role in regulating lipid metabolism and insulin sensitivity.

KEYWORDS:

Adipose Tissue Metabolism; Basic Helix-loop-helix Transcription Factor (bHLH); Fatty Acid Oxidation; Glucose Metabolism; Obesity; Peroxisome Proliferator-activated Receptor γ Coactivator 1-α (PGC-1a) (PPARGC1A); Sirtuin 1 (SIRT1)

PMID:
25190816
PMCID:
PMC4200265
DOI:
10.1074/jbc.M114.571679
[Indexed for MEDLINE]
Free PMC Article

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