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Diabetologia

Erschienen in:

01.10.2006 | Article

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

verfasst von: W. T. Festuccia, M. Laplante, M. Berthiaume, Y. Gélinas, Y. Deshaies

Erschienen in: Diabetologia | Ausgabe 10/2006

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Abstract

Aims/hypothesis

The aim of this study was to investigate the effect and mechanisms of action of in vivo peroxisome proliferator-activated receptor γ (PPARγ) activation on white adipose tissue (WAT) lipolysis and NEFA metabolism.

Materials and methods

Study rats were treated for 7 days with 15 mg/kg of rosiglitazone per day; control rats were not treated. After a 6-h fast, lipolysis and levels of mRNA for lipases were assessed in explants from various adipose depots.

Results

Rosiglitazone markedly increased basal and noradrenaline (norepinephrine)-stimulated glycerol and NEFA release from WAT explants, and amplified their inhibition by insulin. Primary adipocytes isolated from PPARγ agonist-treated rats were also more responsive to noradrenaline stimulation expressed per cell, ruling out a contribution of an altered number of mature adipocytes in explants. Rosiglitazone concomitantly increased levels of mRNA transcripts for adipose triglyceride lipase (ATGL) and monoglyceride lipase (MGL) in subcutaneous and visceral WAT, and mRNA for hormone-sensitive lipase (HSL) in subcutaneous WAT. Lipase expression increased within 12 h of in vitro exposure of naïve explants to rosiglitazone, suggesting direct transcriptional activation. In parallel, chronic in vivo treatment with rosiglitazone lowered plasma NEFAs and in WAT its expected stimulatory action on glycerol and NEFA recycling, and on the expression of genes involved in NEFA uptake and retention by WAT, such processes counteracting net NEFA export.

Conclusions/interpretation

These findings demonstrate that, in the face of its plasma NEFA-lowering action, PPARγ agonism stimulates WAT lipolysis, an effect that is compensated by lipid-retaining pathways. The results further suggest that PPARγ agonism stimulates lipolysis by increasing the lipolytic potential, including the expression levels of the genes encoding adipose triglyceride lipase and monoglyceride lipase.

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Fürnsinn C, Waldhäusl W (2002) Thiazolidinediones: metabolic actions in vitro. Diabetologia 45:1211–1223PubMedCrossRef

Kintscher U, Law RE (2005) PPARγ-mediated insulin sensitization: the importance of fat versus muscle. Am J Physiol Endocrinol Metab 288:E287–E291PubMedCrossRef

Ye JM, Dzamko N, Cleasby ME et al (2004) Direct demonstration of lipid sequestration as a mechanism by which rosiglitazone prevents fatty-acid-induced insulin resistance in the rat: comparison with metformin. Diabetologia 47:1306–1313PubMedCrossRef

Oakes ND, Thalen PG, Jacinto SM, Ljung B (2001) Thiazolidinediones increase plasma-adipose tissue FFA exchange capacity and enhance insulin-mediated control of systemic FFA availability. Diabetes 50:1158–1165PubMedCrossRef

Guan HP, Li Y, Jensen MV, Newgard CB, Steppan CM, Lazar MA (2002) A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nat Med 8:1122–1128PubMedCrossRef

Tordjman J, Chauvet G, Quette J, Beale EG, Forest C, Antoine B (2003) Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells. J Biol Chem 278:18785–18790PubMedCrossRef

Kalderon B, Mayorek N, Ben-Yaacov L, Bar-Tana J (2003) Adipose tissue sensitization to insulin induced by troglitazone and MEDICA 16 in obese Zucker rats in vivo. Am J Physiol Endocrinol Metab 284:E795–E803PubMed

Fredrikson G, Belfrage P (1983) Positional specificity of hormone-sensitive lipase from rat adipose tissue. J Biol Chem 258:14253–14256PubMed

Fortier M, Wang SP, Mauriege P et al (2004) Hormone-sensitive lipase-independent adipocyte lipolysis during beta-adrenergic stimulation, fasting, and dietary fat loading. Am J Physiol Endocrinol Metab 287:E282–E288PubMedCrossRef

10.

Haemmerle G, Zimmermann R, Hayn M et al (2002) Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem 277:4806–4815PubMedCrossRef

11.

Okazaki H, Osuga J, Tamura Y et al (2002) Lipolysis in the absence of hormone-sensitive lipase: evidence for a common mechanism regulating distinct lipases. Diabetes 51:3368–3375PubMedCrossRef

12.

Zimmermann R, Strauss JG, Haemmerle G et al (2004) Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306:1383–1386PubMedCrossRef

13.

Villena JA, Roy S, Sarkadi-Nagy E, Kim KH, Sul HS (2004) Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem 279:47066–47075PubMedCrossRef

14.

Jenkins CM, Mancuso DJ, Yan W, Sims HF, Gibson B, Gross RW (2004) Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A₂ family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem 279:48968–48975PubMedCrossRef

15.

Zechner R, Strauss JG, Haemmerle G, Lass A, Zimmermann R (2005) Lipolysis: pathway under construction. Curr Opin Lipidol 16:333–340PubMedCrossRef

16.

Kershaw EE, Hamm JK, Verhagen LA, Peroni O, Katic M, Flier JS (2006) Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes 55:148–157PubMedCrossRef

17.

Mori Y, Murakawa Y, Okada K et al (1999) Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care 22:908–912PubMedCrossRef

18.

Picard F, Auwerx J (2002) PPARγ and glucose homeostasis. Annu Rev Nutr 22:167–197PubMedCrossRef

19.

Willson TM, Lambert MH, Kliewer SA (2001) Peroxisome proliferator-activated receptor gamma and metabolic disease. Annu Rev Biochem 70:341–367PubMedCrossRef

20.

Laplante M, Sell H, MacNaul KL, Richard D, Berger JP, Deshaies Y (2003) PPAR-gamma activation mediates adipose depot-specific effects on gene expression and lipoprotein lipase activity: mechanisms for modulation of postprandial lipemia and differential adipose accretion. Diabetes 52:291–299PubMedCrossRef

21.

Berthiaume M, Sell H, Lalonde J et al (2004) Actions of PPARgamma agonism on adipose tissue remodeling, insulin sensitivity, and lipemia in absence of glucocorticoids. Am J Physiol Regul Integr Comp Physiol 287:R1116–R1123PubMed

22.

Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79:1147–1156PubMedCrossRef

23.

van Harmelen V, Dicker A, Ryden M et al (2002) Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes. Diabetes 51:2029–2036PubMedCrossRef

24.

Mayerson AB, Hundal RS, Dufour S et al (2002) The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 51:797–802PubMedCrossRef

25.

Racette SB, Davis AO, McGill JB, Klein S (2002) Thiazolidinediones enhance insulin-mediated suppression of fatty acid flux in type 2 diabetes mellitus. Metabolism 51:169–174PubMedCrossRef

26.

Tan GD, Fielding BA, Currie JM et al (2005) The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia 48:83–95PubMedCrossRef

27.

Lake AC, Sun Y, Li JL et al (2005) Expression, regulation, and triglyceride hydrolase activity of adiponutrin family members. J Lipid Res 46:2477–2487PubMedCrossRef

28.

Fredrikson G, Tornqvist H, Belfrage P (1986) Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol. Biochim Biophys Acta 876:288–293PubMed

29.

McTernan PG, Harte AL, Anderson LA et al (2002) Insulin and rosiglitazone regulation of lipolysis and lipogenesis in human adipose tissue in vitro. Diabetes 51:1493–1498PubMedCrossRef

30.

Teruel T, Hernandez R, Rial E, Martin-Hidalgo A, Lorenzo M (2005) Rosiglitazone up-regulates lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1, and down-regulates insulin-induced fatty acid synthase gene expression in brown adipocytes of Wistar rats. Diabetologia 48:1180–1188PubMedCrossRef

31.

Deng T, Shan S, Li P-P et al (2005) Peroxisome proliferator-activated receptor gamma transcriptionally up-regulates hormone-sensitive lipase via the involvement of Sp1. Endocrinology 147:875–884PubMedCrossRef

32.

Dalen KT, Schoonjans K, Ulven SM et al (2004) Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-gamma. Diabetes 53:1243–1252PubMedCrossRef

33.

Rosenbaum SE, Greenberg AS (1998) The short- and long-term effects of tumor necrosis factor-α and BRL 49653 on peroxisome proliferator-activated receptor (PPAR)γ2 gene expression and other adipocyte genes. Mol Endocrinol 12:1150–1160PubMedCrossRef

34.

Bartness TJ, Kay Song C, Shi H, Bowers RR, Foster MT (2005) Brain-adipose tissue cross talk. Proc Nutr Soc 64:53–64PubMedCrossRef

35.

Sell H, Berger JP, Samson P et al (2004) Peroxisome proliferator-activated receptor γ agonism increases the capacity for sympathetically mediated thermogenesis in lean and ob/ob mice. Endocrinology 145:3925–3934PubMedCrossRef

36.

Rosenstock M, Greenberg AS, Rudich A (2001) Distinct long-term regulation of glycerol and non-esterified fatty acid release by insulin and TNF-alpha in 3T3-L1 adipocytes. Diabetologia 44:55–62PubMedCrossRef

37.

Reshef L, Olswang Y, Cassuto H et al (2003) Glyceroneogenesis and the triglyceride/fatty acid cycle. J Biol Chem 278:30413–30416PubMedCrossRef

38.

Coort SL, Coumans WA, Bonen A, van der Vusse GJ, Glatz JF, Luiken JJ (2005) Divergent effects of rosiglitazone on protein-mediated fatty acid uptake in adipose and in muscle tissues of Zucker rats. J Lipid Res 46:1295–1302PubMedCrossRef

39.

Frohnert BI, Hui TY, Bernlohr DA (1999) Identification of a functional peroxisome proliferator-responsive element in the murine fatty acid transport protein gene. J Biol Chem 274:3970–3977PubMedCrossRef

40.

Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM (1994) mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8:1224–1234PubMed

Titel: PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control
verfasst von: W. T. Festuccia
M. Laplante
M. Berthiaume
Y. Gélinas
Y. Deshaies
Publikationsdatum: 01.10.2006
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 10/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0336-y

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Materials and methods

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