A Pro12Ala substitution in PPARγ2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity (original) (raw)

• Tontonoz, P., Hu, E. & Spiegelman, B.M. Stimulation of adipogenesis in fibroblasts by PPAR γ 2, a lipid-activated transcription factor. Cell 79, 1147–1156 (1994).
  Article CAS Google Scholar
• Tontonoz, P. Hu, E., Graves, R.A., Budavari, A.I. & Spiegelman, B.M. mPPAR γ 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 8, 1224– 1234 (1994).
  Article CAS Google Scholar
• Tontonoz, P. & Spiegelman, B.M. Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor γ. Curr. Opin. Genet. Dev. 5, 571– 576 (1995).
  Article CAS Google Scholar
• Fajas, L. et al. The organization, promoter analysis, and expression of the human PPARγ gene. J. Biol. Chem. 272, 18779–18789 (1997).
  Article CAS Google Scholar
• Werman, A. et al. Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor γ (PPARγ). Differential activity of PARγ 1 and -2 isoforms and influence of insulin. J. Biol. Chem. 272, 20230–20235 (1997).
  Article CAS Google Scholar
• Vidal-Puig, A. et al. Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest. 99, 2416–2422 (1997).
  Article CAS Google Scholar
• Kahn, C.R. Diabetes. Causes of insulin resistance. Nature 373, 384–385 (1995).
  Article CAS Google Scholar
• Spiegelman, B.M. & Flier, J.S. Adipogenesis and obesity: rounding out the big picture. Cell 87, 377–389 (1996).
  Article CAS Google Scholar
• Auwerx, J., Martin, G., Guerre-Millo, M. & Staels, B. Transcription, adipocyte differentiation, and obesity. J. Mol. Med. 74, 347–352 (1996).
  Article CAS Google Scholar
• Hotamisligil, G.S., Shargill, N.S. & Spiegelman, B.M. Adipose expression of tumor necrosis factor-γ: direct role in obesity-linked insulin resistance. Science 259, 87–91 (1993).
  Article CAS Google Scholar
• Kliewer, S.A. et al., A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation. Cell 83, 813–819 (1995).
  Article CAS Google Scholar
• Lehmann, J.M. et al., An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J. Biol. Chem. 270, 12953–12956 (1995).
  Article CAS Google Scholar
• Saltiel, A.R. & Olefsky, J.M. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 45, 1661–1669 (1996).
  Article CAS Google Scholar
• Bouchard, C. Genetics of obesity: an update on molecular markers. Int. J. Obes. Rel. Metab. Disord. 19, S10–S13 (1995).
  Google Scholar
• Meirhaeghe, A. et al. A genetic polymorphism of the peroxisome proliferator-activated receptor γ gene influences plasma leptin levels in obese humans. Hum. Mol. Genet. 7, 435–440 (1998).
  Article CAS Google Scholar
• Laakso, M. et al. Atherosclerotic vascular disease and its risk factors in non-insulin-dependent diabetic and nondiabetic subjects in Finland. Diabetes Care 11, 449–463 (1988).
  Article CAS Google Scholar
• Fujimoto, W.Y., Bergstrom, R.W., Newell-Morris, L. & Leonetti, D.L. Nature and nurture in the etiology of type 2 diabetes mellitus in Japanese Americans. Diabetes Metab. Rev. 5, 607– 625 (1989).
  Article CAS Google Scholar
• Schoonjans, K. et al. PPARγ and PPARγ activators direct a distinct tissue specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 15, 5336– 5348 (1996).
  Article CAS Google Scholar
• Nolan, J.J., Ludvik, B., Beerdsen, P., Joyce, M. & Olefsky, J. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N. Engl. J. Med. 331, 1188–1193 (1994).
  Article CAS Google Scholar
• Burant, C.F. et al. Troglitazone action in independent of adipose tissue. J. Clin. Invest. 100, 2900–2908 (1997).
  Article CAS Google Scholar
• Reaven, G.M. Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988).
  Article CAS Google Scholar
• Chagnon, Y.C., Perusse, L. & Bouchard, C. The human obesity gene map: the 1997 update. Obesity Res. 6, 76–92 (1998).
  Article CAS Google Scholar
• Norman, R.A. et al. Genomewide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome 11q21-q22. Am. J. Hum. Genet. 60, 166–173 (1997).
  CAS PubMed PubMed Central Google Scholar
• Beamer, B.A. et al. Chromosomal localization and partial genomic structure of the human peroxisome proliferator activated receptor-γ (hPPAR γ) gene. Biochem. Biophys. Res. Commun. 233, 756–759 (1997).
  Article CAS Google Scholar
• Hanis, C.L. et al. A genome-wide search for human non-insulin-dependent (type2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nature Genet. 13, 161–166 (1996).
  Article CAS Google Scholar
• Mykkänen, L., Laakso, M., Uusitupa, M. & Pyörälä, K. Prevalence of diabetes and impaired glucose tolerance in elderly subjects and their association with obesity and family history of diabetes. Diabetes Care 13, 1099–1105 (1990).
  Article Google Scholar
• Nevin, D., Deeb, S. & Brunzell, J. The LPL gene in individuals with familial combined hyperlipidemia and decreased LPL activity. Arterioscler. Thromb. 14, 869–873 (1994).
  Article CAS Google Scholar
• Vu-Dac, N. et al. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J. Clin. Invest. 96, 741–750 (1995).
  Article CAS Google Scholar
• Fried, M.G. & Crothers, D.M. CAP and RNA polymerase interactions with the lac binding stoichiometry and long range effects. Nucleic Acids Res. 11, 141–158 (1983).
  Article CAS Google Scholar
• Mykkanen, L. et al. Is there a sex difference in the association of plasma insulin level and insulin sensitivity with serum lipids and lipoproteins? Metabolism 43, 523–528 (1994).
  Article CAS Google Scholar