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

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


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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / metabolism*
  • Animals
  • Calorimetry
  • Energy Metabolism
  • Fatty Acids / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Genotype
  • Glucose / metabolism
  • Glucose Intolerance / metabolism*
  • Glucose Tolerance Test
  • Inhibitor of Differentiation Protein 1 / genetics*
  • Insulin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Oxygen / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Sirtuin 1 / metabolism*
  • Transcription Factors / metabolism*


  • Fatty Acids
  • Idb1 protein, mouse
  • Inhibitor of Differentiation Protein 1
  • Insulin
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Transcription Factors
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Glucose
  • Oxygen