Induction of fatty acid translocase/CD36, peroxisome proliferator-activated receptor-gamma 2, leptin, uncoupling proteins 2 and 3, and tumor necrosisfactor-alpha gene expression in human subcutaneous fat by lipid infusion

Little is known about the mechanisms involved in the preferential channelin g of different fuels to fat and how the target tissue participates in this process. Dietary fatty acids have been shown to act as signaling molecules that bind and activate a new class of nuclear receptors, the peroxisome pro liferator-activated receptors (PPARs). PPAR-gamma is particularly interesti ng because it may have the potential to link particular fatty acids with a program of gene expression involved in lipid storage and metabolism. We inv estigated whether a nutrient-sensing pathway is activated by an increased a vailability of lipid fuels in nine normal weight male volunteers. Using rev erse transcriptase-polymerase chain reaction analysis, the mRNA expression of fatty acid translocase (FAT)/CD36, PPAR-gamma 2, leptin, uncoupling prot ein (UCP)-2 and UCP-3, and tumor necrosis factor (TNF)-alpha was investigat ed in gluteal subcutaneous fat biopsies before and after 5 h infusions of s aline or Intralipid (Pharmacia and Upjohn, Milan, Italy) plus heparin, whic h does not modify insulinemia. Marked increases in FAT/CD36 (724 +/- 18%; P < 0.05), PPAR-gamma 2 (200 +/- 8%; P < 0.05), leptin (110 +/- 13%; P < 0.0 5), UCP-2 (120 +/- 7%; P < 0.05), UCP-3 (80 +/- 5%; P < 0.05), and TNF-alph a mRNA (130 +/- 12%; P < 0.05) were observed in comparison with pretreatmen t levels, whereas there was no change after saline infusion. These data sug gest that the in vivo gene expression of FAT/CD36, PPAR-gamma 2, leptin, UC P-2, UCP-3, and TNF-alpha in subcutaneous adipose tissue is regulated by ci rculating lipids independent of insulin and that prolonged hyperlipidemia m ay therefore contribute to increased fat metabolism and storage as a result of the increased expression of these proteins.