Diabetes, Vol 49, Issue 3 319-324, Copyright © 2000 by American Diabetes Association

ARTICLES

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

E Nisoli, MO Carruba, C Tonello, C Macor, G Federspil and R Vettor
Department of Preclinical Sciences, Center for Study and Research on Obesity, L. Sacco Hospital, Univeristy of Milan, Italy. enzo.nisoli@uniml.it

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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. A. Pearen, J. G. Ryall, M. A. Maxwell, N. Ohkura, G. S. Lynch, and G. E. O. Muscat The Orphan Nuclear Receptor, NOR-1, Is a Target of {beta}-Adrenergic Signaling in Skeletal Muscle Endocrinology, November 1, 2006; 147(11): 5217 - 5227. [Abstract] [Full Text] [PDF]

				P. K. Chelikani, D. H. Keisler, and J. J. Kennelly Response of Plasma Leptin Concentration to Jugular Infusion of Glucose or Lipid Is Dependent on the Stage of Lactation of Holstein Cows J. Nutr., December 1, 2003; 133(12): 4163 - 4171. [Abstract] [Full Text] [PDF]

				P. N. Black and C. C. DiRusso Transmembrane Movement of Exogenous Long-Chain Fatty Acids: Proteins, Enzymes, and Vectorial Esterification Microbiol. Mol. Biol. Rev., September 1, 2003; 67(3): 454 - 472. [Abstract] [Full Text] [PDF]

				D. Cameron-Smith, L. M Burke, D. J Angus, R. J Tunstall, G. R Cox, A. Bonen, J. A Hawley, and M. Hargreaves A short-term, high-fat diet up-regulates lipid metabolism and gene expression in human skeletal muscle Am. J. Clinical Nutrition, February 1, 2003; 77(2): 313 - 318. [Abstract] [Full Text] [PDF]

				S. J. Crozier, D. R. Bolster, A. K. Reiter, S. R. Kimball, and L. S. Jefferson beta -Oxidation of free fatty acids is required to maintain translational control of protein synthesis in heart Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1144 - E1150. [Abstract] [Full Text] [PDF]

				G. Patane, M. Anello, S. Piro, R. Vigneri, F. Purrello, and A. M. Rabuazzo Role of ATP Production and Uncoupling Protein-2 in the Insulin Secretory Defect Induced by Chronic Exposure to High Glucose or Free Fatty Acids and Effects of Peroxisome Proliferator-Activated Receptor-{gamma} Inhibition Diabetes, September 1, 2002; 51(9): 2749 - 2756. [Abstract] [Full Text] [PDF]

				A. V. Greco, G. Mingrone, A. Giancaterini, M. Manco, M. Morroni, S. Cinti, M. Granzotto, R. Vettor, S. Camastra, and E. Ferrannini Insulin Resistance in Morbid Obesity: Reversal With Intramyocellular Fat Depletion Diabetes, January 1, 2002; 51(1): 144 - 151. [Abstract] [Full Text] [PDF]

				A. L. Hevener, D. Reichart, A. Janez, and J. Olefsky Thiazolidinedione Treatment Prevents Free Fatty Acid-Induced Insulin Resistance in Male Wistar Rats Diabetes, October 1, 2001; 50(10): 2316 - 2322. [Abstract] [Full Text]

				N. Stefan, A. Fritsche, H. Häring, and M. Stumvoll Effect of Experimental Elevation of Free Fatty Acids on Insulin Secretion and Insulin Sensitivity in Healthy Carriers of the Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor-{gamma}2 Gene Diabetes, May 1, 2001; 50(5): 1143 - 1148. [Abstract] [Full Text]

				R. Fabris, E. Nisoli, A. M. Lombardi, C. Tonello, R. Serra, M. Granzotto, I. Cusin, F. Rohner-Jeanrenaud, G. Federspil, M. O. Carruba, et al. Preferential Channeling of Energy Fuels Toward Fat Rather Than Muscle During High Free Fatty Acid Availability in Rats Diabetes, March 1, 2001; 50(3): 601 - 608. [Abstract] [Full Text]

				J. A. Johnson, S. K. Fried, F. X. Pi-Sunyer, and J. B. Albu Impaired insulin action in subcutaneous adipocytes from women with visceral obesity Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E40 - E49. [Abstract] [Full Text] [PDF]