Reduced expression of PGC-1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance.
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.
Hammarstedt
A
A
The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Jansson
P-A
PA
Wesslau
C
C
Yang
X
X
Smith
U
U
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013223:Statistics as Topic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014475:Uncoupling Agents / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D051275:Glucose Transporter Type 4; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C495692:SLC2A4 protein, human; D014157:Transcription Factors; C000604371:UCP1 protein, human; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1