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The PPARγ ligand rosiglitazone influences triacylglycerol metabolism in non-obese males, without increasing the transcriptional activity of PPARγ in the subcutaneous adipose tissue

  • Annemiek M. C. P. Joosen (a1), Arjen H. F. Bakker (a2), Sander Kersten (a3) and Klaas R. Westerterp (a1)

Abstract

PPARγ is obligatory for fat mass generation and is thought to determine the amount of TAG stored per fat cell. We investigated whether ligand availability for PPARγ is rate limiting in fat mass generation and substrate metabolism. Twenty healthy men (20–29 years) were randomly assigned to receive the PPARγ ligand rosiglitazone (RSG) (8 mg/d) (n 10) or a placebo (n 10) during a stay of 7 d in a respiration chamber. Food intake was ad libitum, resulting in positive energy balances of 32·2 MJ (placebo) and 44·7 MJ (RSG). Fat cell size and expression of PPARγ, adipocyte fatty acid-binding protein (aP2), adipsin, adiponectin and fasting-induced adipose factor (FIAF) were determined in subcutaneous abdominal fat biopsies. The total amount of fat stored and the amount of TAG per fat cell were not different between groups. For the entire group, fat cell size was decreased after overeating (P = 0·02). FIAF mRNA levels were decreased after overeating in the RSG group (P = 0·01), with a trend towards a decrease in the placebo group. Unexpectedly, RSG treatment did not influence the expression levels of PPARγ and of the PPARγ responsive genes aP2, adiponectin and adipsin. In addition, RSG resulted in a larger increase in plasma TAG during overeating than placebo treatment. These results suggest that in healthy, non-obese males the PPARγ ligand RSG influences TAG metabolism, independent of its PPARγ transcriptional activity in the subcutaneous adipose tissue.

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Corresponding author

*Corresponding author: Annemiek M.C.P. Joosen, fax +44 (0)1223 252 765, email amj@mrc-dunn.cam.ac.uk

References

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1Silventoinen, K, Sans, S, Tolonen, H, Monterde, D, Kuulasmaa, K, Kesteloot, H & Tuomilehto, J (2004) Trends in obesity and energy supply in the WHO MONICA Project. Int J Obes Relat Metab Disord 28, 710718.
2Prins, JB & O'Rahilly, S (1997) Regulation of adipose cell number in man. Clinical Science 92, 311.
3Farnier, C, Krief, S, Blache, M, Diot-Dupuy, F, Mory, G, Ferre, P & Bazin, R (2003) Adipocyte functions are modulated by cell size change: potential involvement of an integrin/ERK signalling pathway. Int J Obes Relat Metab Disord 27, 11781186.
4Rosen, ED, Sarraf, P, Troy, AE, Bradwin, G, Moore, K, Milstone, DS, Spiegelman, BM & Mortensen, RM (1999) PPARγ is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4, 611617.
5Evans, RM, Barish, GD & Wang, YX (2004) PPARs and the complex journey to obesity. Nat Med 10, 355361.
6Ristow, M, Muller-Wieland, D, Pfeiffer, A, Krone, W & Kahn, CR (1998) Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med 339, 953959.
7Savage, DB, Tan, GD, Acerini, CL, et al. (2003) Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes 52, 910917.
8Miard, S & Fajas, L (2005) Atypical transcriptional regulators and cofactors of PPARγ. Int J Obes Relat Metab Disord 29, Suppl. 1, S10S12.
9Kliewer, SA, Sundseth, SS, Jones, SA, et al. (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ. Proc Natl Acad Sci USA 94, 43184323.
10Lehmann, JM, Moore, LB, Smith-Oliver, TA, Wilkison, WO, Willson, TM & Kliewer, SA (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPAR γ). J Biol Chem 270, 1295312956.
11Chaput, E, Saladin, R, Silvestre, M & Edgar, AD (2000) Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun 271, 445450.
12Larsen, PJ, Jensen, PB, Sorensen, RV, Larsen, LK, Vrang, N, Wulff, EM & Wassermann, K (2003) Differential influences of peroxisome proliferator-activated receptors γ and -α on food intake and energy homeostasis. Diabetes 52, 22492259.
13Asnani, S, Richard, BC, Desouza, C & Fonseca, V (2003) Is weight loss possible in patients treated with thiazolidinediones? Experience with a low-calorie diet. Curr Med Res Opin 19, 609613.
14Joosen, AM, Bakker, AH, Zorenc, AH, Kersten, S, Schrauwen, P & Westerterp, KR (2006) PPARγ activity in subcutaneous abdominal fat tissue and fat mass gain during short-term overfeeding. Int J Obes (Lond) 30, 302307.
15Chao, L, Marcus-Samuels, B, Mason, MM, Moitra, J, Vinson, C, Arioglu, E, Gavrilova, O & Reitman, ML (2000) Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones. J Clin Invest 106, 12211228.
16Hutley, LJ, Newell, FM, Joyner, JM, Suchting, SJ, Herington, AC, Cameron, DP & Prins, JB (2003) Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation. Eur J Clin Invest 33, 574581.
17Berthiaume, M, Sell, H, Lalonde, J, Gelinas, Y, Tchernof, A, Richard, D & Deshaies, Y (2004) Actions of PPARγ agonism on adipose tissue remodeling, insulin sensitivity, and lipemia in absence of glucocorticoids. Am J Physiol Regul Integr Comp Physiol 287, R1116R1123.
18Tiikkainen, M, Hakkinen, AM, Korsheninnikova, E, Nyman, T, Makimattila, S & Yki-Jarvinen, H (2004) Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 53, 21692176.
19Joosen, AM, Bakker, AH, Gering, MJ & Westerterp, KR (2006) The effect of the PPARγ ligand rosiglitazone on energy balance regulation. Diabetes Metab Res Rev 22, 204210.
20Stunkard, AJ & Messick, S (1985) The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. J Psychosom Res 29, 7183.
21Brouwer, E (1957) On simple formulae for calculating the heat expenditure and the quantities of carbohydrate and fat oxidized in metabolism of men and animals, from gaseous exchange (oxygen intake and carbonic acid output) and urine-N. Acta Physiol Pharmacol Neerl 6, 795802.
22Schoffelen, PF, Westerterp, KR, Saris, WH & Ten Hoor, F (1997) A dual-respiration chamber system with automated calibration. J Appl Physiol 83, 20642072.
23NEVO Foundation, NEVO table. Dutch Food Composition Table (1996) [in Dutch]. The Netherlands Nutrition Center, The Hague, The Netherlands.
24Westerterp, KR, Wouters, L & Marken Lichtenbelt, WDv (1995) The Maastricht protocol for the measurement of body composition and energy expenditure with labeled water. Obes Res 3, 4957.
25Siri, WE (1993) Body composition from fluid spaces and density: analysis of methods. 1961. Nutrition 9, 480491, discussion 480, 492.
26Bakker, AH, Van Dielen, FM, Greve, JW, Adam, JA & Buurman, WA (2004) Preadipocyte number in omental and subcutaneous adipose tissue of obese individuals. Obes Res 12, 488498.
27Chomczynski, P & Sacchi, N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162, 156159.
28Ross, SR, Graves, RA, Greenstein, A, Platt, KA, Shyu, HL, Mellovitz, B & Spiegelman, BM (1990) A fat-specific enhancer is the primary determinant of gene expression for adipocyte P2 in vivo. Proc Natl Acad Sci U S A 87, 95909594.
29Sen, A, Lea-Currie, YR, Sujkowska, D, Franklin, DM, Wilkison, WO, Halvorsen, YD & Gimble, JM (2001) Adipogenic potential of human adipose derived stromal cells from multiple donors is heterogeneous. J Cell Biochem 81, 312319.
30Bogacka, I, Xie, H, Bray, GA & Smith, SR (2004) The effect of pioglitazone on peroxisome proliferator-activated receptor-γ target genes related to lipid storage in vivo. Diabetes Care 27, 16601667.
31Gustafson, B, Jack, MM, Cushman, SW & Smith, U (2003) Adiponectin gene activation by thiazolidinediones requires PPARγ2, but not C/EBPα-evidence for differential regulation of the aP2 and adiponectin genes. Biochem Biophys Res Commun 308, 933939.
32Xia, Z & Cianflone, K (2003) Acylation-stimulating protein precursor proteins in adipose tissue in human obesity. Metabolism 52, 13601366.
33Maeda, N, Takahashi, M, Funahashi, T, et al. (2001) PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50, 20942099.
34Yang, X, Jansson, PA, Nagaev, I, Jack, MM, Carvalho, E, Sunnerhagen, KS, Cam, MC, Cushman, SW & Smith, U (2004) Evidence of impaired adipogenesis in insulin resistance. Biochem Biophys Res Commun 317, 10451051.
35Boden, G, Homko, C, Mozzoli, M, Showe, LC, Nichols, C & Cheung, P (2005) Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. Diabetes 54, 880885.
36Kersten, S, Mandard, S, Tan, NS, Escher, P, Metzger, D, Chambon, P, Gonzalez, FJ, Desvergne, B & Wahli, W (2000) Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J Biol Chem 275, 2848828493.
37Mandard, S, Zandbergen, F, Tan, NS, et al. (2004) The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofibrate treatment. J Biol Chem 279, 3441134420.
38Guan, Y, Hao, C, Cha, DR, et al. (2005) Thiazolidinediones expand body fluid volume through PPAR stimulation of ENaC-mediated renal salt absorption. Nat Med 11, 861866.
39Zhang, H, Zhang, A, Kohan, DE, Nelson, RD, Gonzalez, FJ & Yang, T (2005) Collecting duct-specific deletion of peroxisome proliferator-activated receptor γ blocks thiazolidinedione-induced fluid retention. Proc Natl Acad Sci U S A 102, 94069411.
40Sotiropoulos, KB, Clermont, A, Yasuda, Y, et al. (2006) Adipose-specific effect of rosiglitazone on vascular permeability and protein kinase C activation: novel mechanism for PPARγ agonist's effects on edema and weight gain. Faseb J 20, 12031205.
41Kubota, N, Terauchi, Y, Miki, H, et al. (1999) PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 4, 597609.
42LeBrasseur, NK, Kelly, M, Tsao, TS, Farmer, SR, Saha, AK, Ruderman, NB & Tomas, E (2006) Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues. Am J Physiol Endocrinol Metab 291, E175E181.
43Diradourian, C, Girard, J & Pegorier, JP (2005) Phosphorylation of PPARs: from molecular characterization to physiological relevance. Biochimie 87, 3338.

Keywords

The PPARγ ligand rosiglitazone influences triacylglycerol metabolism in non-obese males, without increasing the transcriptional activity of PPARγ in the subcutaneous adipose tissue

  • Annemiek M. C. P. Joosen (a1), Arjen H. F. Bakker (a2), Sander Kersten (a3) and Klaas R. Westerterp (a1)

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