Downregulation of ADIPOQ and PPARγ2 gene expression in subcutaneous adipose tissue of obese adolescents with hepatic steatosis.
Hepatic steatosis is associated with hypoadiponectinemia. The mechanism(s) resulting in lower serum adiponectin levels in obese adolescents with fatty liver is unknown. In two groups of equally obese adolescents, but discordant for hepatic fat content, we measured adiponectin, leptin, peroxisome proliferator-activated receptor γ 2 (PPARγ2) and tumor necrosis factor-α (TNFα) gene expression in the abdominal subcutaneous adipose tissue (SAT). Twenty six adolescents with similar degrees of obesity underwent a subcutaneous periumbilical adipose tissue biopsy, in addition to metabolic (oral glucose tolerance test, and hyperinsulinemic--euglycemic clamp), and imaging studies (magnetic resonance imaging (MRI), DEXA). Using quantitative real-time-PCR; adiponectin, PPARγ2, TNFα, and leptin mRNA were measured. Based on a hepatic fat content (hepatic fat fraction, HFF) >5.5%, measured by fast MRI, the subjects were divided into low and high HFF group. In addition to the hypoadiponectinemia in the high HFF group, we found that the expression of adiponectin as well as PPARγ2 in the SAT was significantly decreased in this group. No differences were noted for TNFα and leptin plasma or mRNA levels between the groups. An inverse relationship was observed between adiponectin or PPARγ2 expression and hepatic fat content, whereas, adiponectin expression was positively related to PPARγ2 expression. Independent of overall obesity, a reduced expression of adiponectin and PPARγ2 in the abdominal SAT is associated with high liver fat content, as well as with insulin resistance in obese adolescents.
Kursawe
Romy
R
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Narayan
Deepak
D
Cali
Anna M G
AM
Shaw
Melissa
M
Pierpont
Bridget
B
Shulman
Gerald I
GI
Caprio
Sonia
S
D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000293:Adolescent; D015536:Down-Regulation; D005234:Fatty Liver / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000097:blood / Q000235:genetics*; D050151:Subcutaneous Fat / Q000378:metabolism*
D052242:Adiponectin; D047495:PPAR gamma