Human Subcutaneous Fat by Lipid Infusion

Little is known about the mechanisms involved in the preferential channeling 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 proliferatora c t ivated receptors (PPARs). PPA Ris particularly interesting because it may have the potential to link particular fatty acids with a program of gene expression involved in lipid storage and metabolism. We investigated whether a nutrient-sensing pathway is activated by an increased availability of lipid fuels in nine normal weight male volunteers. Using reverse transcriptase–polymerase chain reaction analysis, the mRNA expression of fatty acid translocase (FAT ) / C D 3 6 , P PA R2, leptin, uncoupling protein (UCP)-2 and U C P-3, and tumor necrosis factor (TNF)was investigated in gluteal subcutaneous fat biopsies before and after 5 h infusions of saline or Intralipid (Pharmacia and Upjohn, Milan, Italy) plus heparin, which does not modify insulinemia. Marked increases in FAT/CD36 (724 ± 18%; P < 0.05), PPA R2 (200 ± 8%; P < 0.05), leptin (110 ± 13%; P < 0.05), UCP-2 (120 ± 7%; P < 0.05), UCP-3 (80 ± 5%; P < 0.05), and TNFmRNA (130 ± 12%; P < 0.05) were observed in comparison with pretreatment levels, whereas there was no change after saline infusion. These data suggest that the in vivo gene expression of FAT / C D 3 6 , P PA R2, leptin, UCP-2, UCP-3, and TNFin subcutaneous adipose tissue is regulated by circulating lipids independent of insulin and that prolonged hyperlipidemia may therefore contribute to increased fat metabolism and storage as a result of the increased expression of these proteins. D i a b e t e s 4 9 :3 1 9–324, 2000