- Dreyer C, Krey G, Keller H et al.: Control of the peroxisomal b-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68, 879–887 (1992).
- Discovery of PPARγ and other members of the PPAR family
- Desvergne B, Wahli W: Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev. 20, 649–688 (1999).
- Zhu Y, Qi C, Korenberg JR et al.: Structural organization of mouse peroxisome proliferator-activated receptor g (mPPAR g) gene: alternative promoter use and different splicing yield two mPPAR g isoforms. Proc. Natl Acad. Sci. USA 92, 7921–7925 (1995).
- Larsen TM, Toubro S, Astrup A: PPARγ agonists in the treatment of Type II diabetes: is increased fatness commensurate with long-term efficacy? Int. J. Obes. Relat. Metab. Disord. 27, 147–161 (2003).
- Ferre P: The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53(Suppl. 1), S43–S50 (2004).
- Bouaboula M, Hilairet S, Marchand J et al.: Anandamide induced PPARγ transcriptional activation and 3T3-L1 preadipocyte differentiation. Eur. J. Pharmacol. 517, 174–181 (2005).
- Beekum O, Fleskens V, Kalkhoven E: Posttranslational modifications of PPAR-g: fine-tuning the metabolic master regulator. Obesity (Silver Spring) 17, 213–219 (2009).
- Diradourian C, Girard J, Pegorier JP: Phosphorylation of PPARs: from molecular characterization to physiological relevance. Biochimie 87, 33–38 (2005).
- Lonard DM, Lanz RB, O’Malley BW: Nuclear receptor coregulators and human disease. Endocr. Rev. 28, 575–587 (2007).
- Lonard DM, O’Malley BW: Nuclear receptor coregulators: judges, juries, and executioners of cellular regulation. Mol. Cell 27, 691–700 (2007).
- Rochette-Egly C: Dynamic combinatorial networks in nuclear receptor-mediated transcription. J. Biol. Chem. 280, 32565–32568 (2005).
- Feige JN, Auwerx J: Transcriptional coregulators in the control of energy homeostasis. Trends Cell. Biol. 17, 292–301 (2007).
- Heikkinen S, Auwerx J, Argmann CA: PPARγ in human and mouse physiology. Biochim. Biophys. Acta 1771, 999–1013 (2007).
- Imai T, Takakuwa R, Marchand S et al.: Peroxisome proliferator-activated receptor g is required in mature white and brown adipocytes for their survival in the mouse. Proc. Natl Acad. Sci. USA 101, 4543–4547 (2004).
- Demonstration of the essential role of PPARγ in the survival of mature adipocytes.
- Grimaldi PA: The roles of PPARs in adipocyte differentiation. Prog. Lipid Res. 40, 269–281 (2001).
- Rosen ED, MacDougald OA: Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 7, 885–896 (2006).
- Tontonoz P, Spiegelman BM: Fat and beyond: the diverse biology of PPARg. Annu. Rev. Biochem. 77, 289–312 (2008).
- Agostini M, Schoenmakers E, Mitchell C et al.: Non-DNA binding, dominant-negative, human PPARγ mutations cause lipodystrophic insulin resistance. Cell. Metab. 4, 303–311 (2006).
- Barroso I, Gurnell M, Crowley VE et al.: Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402, 880–883 (1999).
- Savage DB, Agostini M, Barroso I et al.: Digenic inheritance of severe insulin resistance in a human pedigree. Nat. Genet. 31, 379–384 (2002).
- Rosen ED, Sarraf P, Troy AE et al.: PPAR g is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4, 611–617 (1999).
- Mudaliar S, Chang AR, Henry RR: Thiazolidinediones, peripheral edema, and Type 2 diabetes: incidence, pathophysiology, and clinical implications. Endocr. Pract. 9, 406–416 (2003).
- Miyazaki Y, Mahankali A, Matsuda M et al.: Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in Type 2 diabetic patients. J. Clin. Endocrinol. Metab. 87, 2784–2791 (2002).
- First study to demonstrate the association between fat redistribution from visceral to subcutaneous fat and improvement in insulin sensitivity in humans treated with PPARγ ligand.
- Despres JP, Lemieux I: Abdominal obesity and metabolic syndrome. Nature 444, 881–887 (2006).
- Yang X, Smith U: Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer? Diabetologia 50, 1127–1139 (2007).
- Wajchenberg BL: Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr. Rev. 21, 697–738 (2000).
- Kim JY, van de Wall E, Laplante M et al.: Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J. Clin. Invest. 117, 2621–2637 (2007).
- Extensive evaluation of the mechanisms involved in the fat redistribution induced by PPARγ ligand treatment.
- Yamauchi T, Kamon J, Waki H et al.: The mechanisms by which both heterozygous peroxisome proliferator-activated receptor g (PPARg) deficiency and PPARγ agonist improve insulin resistance. J. Biol. Chem. 276, 41245–41254 (2001).
- Takamura T, Nohara E, Nagai Y, Kobayashi K: Stage-specific effects of a thiazolidinedione on proliferation, differentiation and PPARγ mRNA expression in 3T3-L1 adipocytes. Eur. J. Pharmacol. 422, 23–29 (2001).
- Vernochet C, Milstone DS, Iehle C et al.: PPARg-dependent and PPARg-independent effects on the development of adipose cells from embryonic stem cells. FEBS Lett. 510, 94–98 (2002).
- Niesler CU, Siddle K, Prins JB: Human preadipocytes display a depot-specific susceptibility to apoptosis. Diabetes 47, 1365–1368 (1998).
- Adams M, Montague CT, Prins JB et al.: Activators of peroxisome proliferator-activated receptor g have depot-specific effects on human preadipocyte differentiation. J. Clin. Invest. 100, 3149–3153 (1997).
- Kahn SE, Hull RL, Utzschneider KM: Mechanisms linking obesity to insulin resistance and Type 2 diabetes. Nature 444, 840–846 (2006).
- Laplante M, Sell H, MacNaul KL, Richard D, Berger JP, Deshaies Y: PPAR-g 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, 291–299 (2003).
- Demonstration of the essential role of PPARγ in the differentiation of preadipocytes into mature adipocytes and adipose tissue formation.
- Barak Y, Nelson MC, Ong ES et al.: PPAR g is required for placental, cardiac, and adipose tissue development. Mol. Cell 4, 585–595 (1999).
- Kubota N, Terauchi Y, Miki H et al.: PPAR g mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol. Cell 4, 597–609 (1999).
- Medina-Gomez G, Gray SL, Yetukuri L et al.: PPAR g 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 3, E64 (2007).
- Demonstrates the protective effects of enhanced fat deposition and expansion of subcutaneous adipose depot against development of insulin resistance and metabolic syndrome.
- Harman-Boehm I, Bluher M, Redel H et al.: Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J. Clin. Endocrinol. Metab. 92, 2240–2247 (2007).
- Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ: The biology of white adipocyte proliferation. Obes. Rev. 2, 239–254 (2001).
- Demonstration of the essential role of the PPARg2 isoform in the ability of adipose tissue to expand in response to high-fat feeding.
- Lehmann JM, Moore LB, Smith-Oliver TA et al.: An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor g (PPAR g). J. Biol. Chem. 270, 12953–12956 (1995).
- Semple RK, Chatterjee VK, O’Rahilly S: PPAR g and human metabolic disease. J. Clin. Invest. 116, 581–589 (2006).
- Excellent review on the regulation of white adipocyte proliferation.
- Okuno A, Tamemoto H, Tobe K et al.: Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J. Clin. Invest. 101, 1354–1361 (1998).
- de Souza CJ, Eckhardt M, Gagen K et al.: Effects of pioglitazone on adipose tissue remodeling within the setting of obesity and insulin resistance. Diabetes 50, 1863–1871 (2001).
- First demonstration of a depot-specific modulation of lipoprotein lipase activity by PPARγ ligands in the context of fat redistribution from visceral to subcutaneous fat.
- Festuccia WT, Blanchard PG, Turcotte V et al.: Depot-specific effects of the PPARγ agonist rosiglitazone on adipose tissue glucose uptake and metabolism. J. Lipid Res. 50, 1185–1194 (2009).
- Extensive depot specific analysis of the effects of PPARγ ligand on glucose uptake and intracellular fate in visceral and subcutaneous depots.
- Donkor J, Sariahmetoglu M, Dewald J, Brindley DN, Reue K: Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns. J. Biol. Chem. 282, 3450–3457 (2007).
- Yao-Borengasser A, Rasouli N, Varma V et al.: Lipin expression is attenuated in adipose tissue of insulin-resistant human subjects and increases with peroxisome proliferator-activated receptor g activation. Diabetes 55, 2811–2818 (2006).
- Reue K, Brindley DN: Thematic review series: glycerolipids. Multiple roles for lipins/ phosphatidate phosphatase enzymes in lipid metabolism. J. Lipid Res. 49, 2493–2503 (2008).
- DiGirolamo M, Newby FD, Lovejoy J: Lactate production in adipose tissue: a regulated function with extra-adipose implications. FASEB J. 6, 2405–2412 (1992).
- Anghel SI, Bedu E, Vivier CD et al.: Adipose tissue integrity as a prerequisite for systemic energy balance: a critical role for peroxisome proliferator-activated receptor g. J. Biol. Chem. 282, 29946–29957 (2007).
- Guan HP, Li Y, Jensen MV, Newgard CB, Steppan CM, Lazar MA: A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nat. Med. 8, 1122–1128 (2002).
- Tontonoz P, Hu E, Devine J, Beale EG, Spiegelman BM: PPAR g 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol. Cell Biol. 15, 351–357 (1995).
- Festuccia WT, Laplante M, Berthiaume M, Gelinas Y, Deshaies Y: PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control. Diabetologia 49, 2427–2436 (2006).
- Extensive depot-specific analysis of the effects of PPARγ ligand on lipolysis and triacylglycerol–fatty acid cycling.
- Kershaw EE, Schupp M, Guan HP et al.: PPARγ regulates adipose triglyceride lipase in adipocytes in vitro and in vivo. Am. J. Physiol. Endocrinol. Metab. 293, E1736–E1745 (2007).
- Oakes ND, Thalen PG, Jacinto SM, Ljung B: Thiazolidinediones increase plasma–adipose tissue FFA exchange capacity and enhance insulin-mediated control of systemic FFA availability. Diabetes 50, 1158–1165 (2001).
- Extensive evaluation of in vivo fatty acid metabolism and flux among body tissues in rodents treated with PPARγ ligands.
- Koutsari C, Jensen MD: Thematic review series: Patient-oriented research. Free fatty acid metabolism in human obesity. J. Lipid Res. 47, 1643–1650 (2006).
- Newsholme EA: Reflections on the mechanism of action of hormones. FEBS Lett. 117, K121–K134 (1980).
- Brooks B, Arch JR, Newsholme EA: Effects of hormones on the rate of the triacylglycerol/ fatty acid substrate cycle in adipocytes and epididymal fat pads. FEBS Lett. 146, 327–330 (1982).
- Kalderon B, Mayorek N, Ben-Yaacov L, Bar-Tana J: Adipose tissue sensitization to insulin induced by troglitazone and MEDICA 16 in obese Zucker rats in vivo. Am. J. Physiol. Endocrinol. Metab. 284, E795–E803 (2003).
- Miyoshi H, Shulman GI, Peters EJ, Wolfe MH, Elahi D, Wolfe RR: Hormonal control of substrate cycling in humans. J. Clin. Invest. 81, 1545–1555 (1988).
- Wolfe RR, Klein S, Carraro F, Weber JM: Role of triglyceride–fatty acid cycle in controlling fat metabolism in humans during and after exercise. Am. J. Physiol. 258, E382–E389 (1990).
- Frayn KN, Langin D, Karpe F: Fatty acid-induced mitochondrial uncoupling in adipocytes is not a promising target for treatment of insulin resistance unless adipocyte oxidative capacity is increased. Diabetologia 51, 394–397 (2008).
- Harper RD, Saggerson ED: Factors affecting fatty acid oxidation in fat cells isolated from rat white adipose tissue. J. Lipid Res. 17, 516–526 (1976).
- Wilson-Fritch L, Nicoloro S, Chouinard M et al.: Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J. Clin. Invest. 114, 1281–1289 (2004).
- Boden G, Homko C, Mozzoli M, Showe LC, Nichols C, Cheung P: Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. Diabetes 54, 880–885 (2005).
- Bogacka I, Xie H, Bray GA, Smith SR: Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 54, 1392–1399 (2005).
- Cannon B, Nedergaard J: Brown adipose tissue: function and physiological significance. Physiol. Rev. 84, 277–359 (2004).
- Cypess AM, Lehman S, Williams G et al.: Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509–1517 (2009).
- Rothwell NJ, Stock MJ: Biological distribution and significance of brown adipose tissue. Comp. Biochem. Physiol. A Comp. Physiol. 82, 745–751 (1985).
- Petrovic N, Shabalina IG, Timmons JA, Cannon B, Nedergaard J: Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist. Am. J. Physiol. Endocrinol. Metab. 295, E287–E296 (2008).
- Festuccia WT, Blanchard PG, Turcotte V et al.: The PPARγ agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R1327–R1335 (2009).
- Laplante M, Festuccia WT, Soucy G et al.: Involvement of adipose tissues in the early hypolipidemic action of PPARγ agonism in the rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R1408–R1417 (2007).
- Sell H, Berger JP, Samson P et al.: Peroxisome proliferator-activated receptor g agonism increases the capacity for sympathetically mediated thermogenesis in lean and ob/ob mice. Endocrinology 145, 3925–3934 (2004).
- Festuccia WT, Oztezcan S, Laplante M et al.: Peroxisome proliferator-activated receptor-g-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status. Endocrinology 149, 2121–2130 (2008).
- Yanase T, Yashiro T, Takitani K et al.: Differential expression of PPAR g1 and g2 isoforms in human adipose tissue. Biochem. Biophys. Res. Commun. 233, 320–324 (1997).
- Lefebvre AM, Laville M, Vega N et al.: Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 47, 98–103 (1998).
- Montague CT, Prins JB, Sanders L et al.: Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 47, 1384–1391 (1998).
- Picard F, Gehin M, Annicotte J et al.: SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell 111, 931–941 (2002).
- Leonardsson G, Steel JH, Christian M et al.: Nuclear receptor corepressor RIP140 regulates fat accumulation. Proc. Natl Acad. Sci. USA 101, 8437–8442 (2004).
- Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K: Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest. 116, 1784–1792 (2006).
Depot specificities of PPARg ligand actions on lipid and glucose metabolism and their implication in PPARg-mediated body fat redistribution
Reprints and Corporate Permissions
Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?
To request a reprint or corporate permissions for this article, please click on the relevant link below:
Academic Permissions
Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?
Obtain permissions instantly via Rightslink by clicking on the button below:
If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.
Related research
People also read lists articles that other readers of this article have read.
Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.
Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.