title: Induction of fatty acid translocase/CD36, peroxisome proliferator-activated receptor-gamma2, leptin, uncoupling proteins 2 and 3, and tumor necrosis factor-alpha gene expression in human subcutaneous fat by lipid infusion.
abstract: 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 proliferator-activated receptors (PPARs). PPAR-gamma is 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)/CD36, PPAR-gamma2, leptin, uncoupling protein (UCP)-2 and UCP-3, and tumor necrosis factor (TNF)-alpha 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), PPAR-gamma2 (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 TNF-alpha mRNA (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/CD36, PPAR-gamma2, leptin, UCP-2, UCP-3, and TNF-alpha in 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.
authors.affiliation: Department of Preclinical Sciences, Center for Study and Research on Obesity, L. Sacco Hospital, Univeristy of Milan, Italy. enzo.nisoli@uniml.it
authors.forename: E
authors.initials: E
authors.lastname: Nisoli
authors.forename: M O
authors.initials: MO
authors.lastname: Carruba
authors.forename: C
authors.initials: C
authors.lastname: Tonello
authors.forename: C
authors.initials: C
authors.lastname: Macor
authors.forename: G
authors.initials: G
authors.lastname: Federspil
authors.forename: R
authors.initials: R
authors.lastname: Vettor
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology*; D000328:Adult; D002081:Buttocks; D018955:CD36 Antigens / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007473:Ion Channels; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D024101:Mitochondrial Proteins; D027361:Organic Anion Transporters; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D054411:Receptors, Leptin; D012867:Skin; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000071256:Uncoupling Protein 1
chemical_list: D018955:CD36 Antigens; D002352:Carrier Proteins; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; C515448:LEPR protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D054411:Receptors, Leptin; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000071256:Uncoupling Protein 1