Reduced expression of PGC-1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance

Biochem Biophys Res Commun. 2003 Feb 7;301(2):578-82. doi: 10.1016/s0006-291x(03)00014-7.

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR gamma) co-activator 1 (PGC-1) regulates glucose metabolism and energy expenditure and, thus, potentially insulin sensitivity. We examined the expression of PGC-1, PPAR gamma, insulin receptor substrate-1 (IRS-1), glucose transporter isoform-4 (GLUT-4), and mitochondrial uncoupling protein-1 (UCP-1) in adipose tissue and skeletal muscle from non-obese, non-diabetic insulin-resistant, and insulin-sensitive individuals. PGC-1, both mRNA and protein, was expressed in human adipose tissue and the expression was significantly reduced in insulin-resistant subjects. The expression of PGC-1 correlated with the mRNA levels of IRS-1, GLUT-4, and UCP-1 in adipose tissue. Furthermore, the adipose tissue expression of PGC-1 and IRS-1 correlated with insulin action in vivo. In contrast, no differential expression of PGC-1, GLUT-4, or IRS-1 was found in the skeletal muscle of insulin-resistant vs insulin-sensitive subjects. The findings suggest that PGC-1 may be involved in the differential gene expression and regulation between adipose tissue and skeletal muscle. The combined reduction of PGC-1 and insulin signaling molecules in adipose tissue implicates adipose tissue dysfunction which, in turn, can impair the systemic insulin response in the insulin-resistant subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Adipose Tissue / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Gene Expression Regulation
  • Glucose Transporter Type 4
  • Humans
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance / physiology*
  • Ion Channels
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondrial Proteins
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism*
  • Muscle Proteins*
  • Muscle, Skeletal / physiology
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction / physiology
  • Statistics as Topic
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Uncoupling Agents / metabolism
  • Uncoupling Protein 1

Substances

  • Carrier Proteins
  • Glucose Transporter Type 4
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Ion Channels
  • Membrane Proteins
  • Mitochondrial Proteins
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • SLC2A4 protein, human
  • Transcription Factors
  • UCP1 protein, human
  • Uncoupling Agents
  • Uncoupling Protein 1
  • peroxisome-proliferator-activated receptor-gamma coactivator-1