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Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids.
Open accessAbstract
The peroxisome proliferator activated receptor (PPAR gamma) plays a key role in adipogenesis and adipocyte gene expression and is the receptor for the thiazolidinedione class of insulin-sensitizing drugs. The tissue expression and potential for regulation of human PPAR gamma gene expression in vivo are unknown. We have cloned a partial human PPAR gamma cDNA, and established an RNase protection assay that permits simultaneous measurements of both PPAR gamma1 and PPAR gamma2 splice variants. Both gamma1 and gamma2 mRNAs were abundantly expressed in adipose tissue. PPAR gamma1 was detected at lower levels in liver and heart, whereas both gamma1 and gamma2 mRNAs were expressed at low levels in skeletal muscle. To examine the hypothesis that obesity is associated with abnormal adipose tissue expression of PPAR gamma, we quantitated PPARgamma mRNA splice variants in subcutaneous adipose tissue of 14 lean and 24 obese subjects. Adipose expression of PPARgamma 2 mRNA was increased in human obesity (14.25 attomol PPAR gamma2/18S in obese females vs 9.9 in lean, P = 0.003). This increase was observed in both male and females. In contrast, no differences were observed in PPAR gamma1/18S mRNA expression. There was a strong positive correlation (r = 0.70, P < 0.001) between the ratio of PPAR gamma2/gamma1 and the body mass index of these patients. We also observed sexually dimorphic expression with increased expression of both PPAR gamma1 and PPAR gamma2 mRNAs in the subcutaneous adipose tissue of women compared with men. To determine the effect of weight loss on PPAR gamma mRNA expression, seven additional obese subjects were fed a low calorie diet (800 Kcal) until 10% weight loss was achieved. Mean expression of adipose PPAR gamma2 mRNA fell 25% (P = 0.0250 after a 10% reduction in body weight), but then increased to pretreatment levels after 4 wk of weight maintenance. Nutritional regulation of PPAR gamma1 was not seen. In vitro experiments revealed a synergistic effect of insulin and corticosteroids to induce PPAR gamma expression in isolated human adipocytes in culture. We conclude that: (a) human PPAR gamma mRNA expression is most abundant in adipose tissue, but lower level expression of both splice variants is seen in skeletal muscle; to an extent that is unlikely to be due to adipose contamination. (b) RNA derived from adipose tissue of obese humans has increased expression of PPAR gamma 2 mRNA, as well as an increased ratio of PPAR gamma2/gamma1 splice variants that is proportional to the BMI; (c) a low calorie diet specifically down-regulates the expression of PPAR gamma2 mRNA in adipose tissue of obese humans; (d) insulin and corticosteroids synergistically induce PPAR gamma mRNA after in vitro exposure to isolated human adipocytes; and (e) the in vivo modulation of PPAR gamma2 mRNA levels is an additional level of regulation for the control of adipocyte development and function, and could provide a molecular mechanism for alterations in adipocyte number and function in obesity.
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Cites
Braissant, O., Foufelle, F., Scotto, C., Dauça, M., & Wahli, W. (1996) · Endocrinology · doi:10.1210/endo.137.1.8536636 · Cited by 2,217
Cited by
Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome
Wajchenberg, B. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0415 · Cited by 2,961
Deeb, S. S., Fajas, L., Nemoto, M., Pihlajamäki, J., Mykkänen, L., Kuusisto, J., Laakso, M., Fujimoto, W., & Auwerx, J. (1998) · Nature Genetics · doi:10.1038/3099 · Cited by 1,319
Varga, T., Czimmerer, Z., & Nagy, L. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.02.014 · Cited by 933
Samuelsson, A.-M., Matthews, P. A., Argenton, M., Christie, M. R., McConnell, J. M., Jansen, E. H. J. M., Piersma, A. H., Ozanne, S. E., Twinn, D. F., Remacle, C., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.101477 · Cited by 923
McKay, L. I., & Cidlowski, J. A. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.4.0375 · Cited by 805
Glucocorticoids and insulin resistance: old hormones, new targets
ANDREWS, R. C., & WALKER, B. R. (1999) · Clinical Science · doi:10.1042/cs0960513 · Cited by 731
Miyazaki, Y., Mahankali, A., Matsuda, M., Mahankali, S., Hardies, J., Cusi, K., Mandarino, L. J., & DeFronzo, R. A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8567 · Cited by 726
Mechanisms of nutritional and hormonal regulation of lipogenesis
Kersten, S. (2001) · The EMBO Reports · doi:10.1093/embo-reports/kve071 · Cited by 700
Bays, H., Mandarino, L., & DeFronzo, R. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030723 · Cited by 664
PPARγ, the ultimate thrifty gene
Auwerx, J. (1999) · Diabetologia · doi:10.1007/s001250051268 · Cited by 612
Tiikkainen, M., Häkkinen, A.-M., Korsheninnikova, E., Nyman, T., Mäkimattila, S., & Yki-Järvinen, H. (2004) · Diabetes · doi:10.2337/diabetes.53.8.2169 · Cited by 524
Peroxisome proliferator-activated receptors: insight into multiple cellular functions
Escher, P., & Wahli, W. (2000) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/s0027-5107(99)00231-6 · Cited by 491
PPARγ as a new therapeutic target in inflammatory bowel diseases
Dubuquoy, L., Rousseaux, C., Thuru, X., Peyrin-Biroulet, L., Romano, O., Chavatte, P., Chamaillard, M., & Desreumaux, P. (2006) · Gut · doi:10.1136/gut.2006.093484 · Cited by 450
Norris, A. W., Chen, L., Fisher, S. J., Szanto, I., Ristow, M., Jozsi, A. C., Hirshman, M. F., Rosen, E. D., Goodyear, L. J., Gonzalez, F. J., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17305 · Cited by 417
Takacs, M. L., & Abbott, B. D. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfl135 · Cited by 396
Di Gregorio, G. B., Yao-Borengasser, A., Rasouli, N., Varma, V., Lu, T., Miles, L. M., Ranganathan, G., Peterson, C. A., McGehee, R. E., & Kern, P. A. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2305 · Cited by 362
Kabir, M., Catalano, K. J., Ananthnarayan, S., Kim, S. P., Van Citters, G. W., Dea, M. K., & Bergman, R. N. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00203.2004 · Cited by 327
Gastaldelli, A., Harrison, S. A., Belfort-Aguilar, R., Hardies, L. J., Balas, B., Schenker, S., & Cusi, K. (2009) · Hepatology · doi:10.1002/hep.23116 · Cited by 285
Effect of thiazolidinediones on body weight in patients with diabetes mellitus
Fonseca, V. (2003) · The American Journal of Medicine · doi:10.1016/j.amjmed.2003.09.005 · Cited by 283
Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons From Animal Models
den Boer, M., Voshol, P. J., Kuipers, F., Havekes, L. M., & Romijn, J. A. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000116217.57583.6e · Cited by 260
Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies
Giorgino, F., Laviola, L., & Eriksson, J. W. (2005) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2004.01385.x · Cited by 230
Kannisto, K., Pietiläinen, K. H., Ehrenborg, E., Rissanen, A., Kaprio, J., Hamsten, A., & Yki-Järvinen, H. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0153 · Cited by 205
Obesity I: Overview and molecular and biochemical mechanisms
Lustig, R. H., Collier, D., Kassotis, C., Roepke, T. A., Kim, M. J., Blanc, E., Barouki, R., Bansal, A., Cave, M. C., Chatterjee, S., et al. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115012 · Cited by 203
Thiazolidinediones improve β-cell function in type 2 diabetic patients
Gastaldelli, A., Ferrannini, E., Miyazaki, Y., Matsuda, M., Mari, A., & DeFronzo, R. A. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00551.2006 · Cited by 200
BMI and BMD: the potential interplay between obesity and bone fragility
Palermo, A., Tuccinardi, D., Defeudis, G., Watanabe, M., D’Onofrio, L., Lauria Pantano, A., Napoli, N., Pozzilli, P., & Manfrini, S. (2016) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph13060544 · Cited by 197
Allen, D. L., Cleary, A. S., Speaker, K. J., Lindsay, S. F., Uyenishi, J., Reed, J. M., Madden, M. C., & Mehan, R. S. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00798.2007 · Cited by 183
Gilde, A. J., & Van Bilsen, M. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01161.x · Cited by 178
Sidell, R. J., Cole, M. A., Draper, N. J., Desrois, M., Buckingham, R. E., & Clarke, K. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1110 · Cited by 165
Alfaradhi, M. Z., Fernandez-Twinn, D. S., Martin-Gronert, M. S., Musial, B., Fowden, A., & Ozanne, S. E. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00049.2014 · Cited by 136
Signalling mechanisms linking hepatic glucose and lipid metabolism
Weickert, M. O., & Pfeiffer, A. F. H. (2006) · Diabetologia · doi:10.1007/s00125-006-0295-3 · Cited by 127
Reprogrammed marrow adipocytes contribute to myeloma-induced bone disease
Liu, H., He, J., Koh, S. P., Zhong, Y., Liu, Z., Wang, Z., Zhang, Y., Li, Z., Tam, B. T., Lin, P., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau9087 · Cited by 113
García-Bueno, B., Madrigal, J. L. M., Pérez-Nievas, B. G., & Leza, J. C. (2008) · Endocrinology · doi:10.1210/en.2007-0482 · Cited by 97
Troglitazone Antagonizes Metabolic Effects of Glucocorticoids in Humans
Willi, S. M., Kennedy, A., Wallace, P., Ganaway, E., Rogers, N. L., & Garvey, W. T. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2895 · Cited by 77
PPARs and the orchestration of metabolic fuel selection
Sugden, M. C., Zariwala, M. G., & Holness, M. J. (2009) · Pharmacological Research · doi:10.1016/j.phrs.2009.03.014 · Cited by 64
Roh, H. C., Kumari, M., Taleb, S., Tenen, D., Jacobs, C., Lyubetskaya, A., Tsai, L. T.-Y., & Rosen, E. D. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101086 · Cited by 62
Ohlsson, C., Hammarstedt, A., Vandenput, L., Saarinen, N., Ryberg, H., Windahl, S. H., Farman, H. H., Jansson, J.-O., Movérare-Skrtic, S., Smith, U., et al. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00093.2017 · Cited by 55
Cabrera-Reyes, F., Parra-Ruiz, C., Yuseff, M. I., & Zanlungo, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.790568 · Cited by 24
Kanda, T., Saegusa, S., Takahashi, T., Sumino, H., Morimoto, S., Nakahashi, T., Iwai, K., & Matsumoto, M. (2007) · International Journal of Cardiology · doi:10.1016/j.ijcard.2006.07.181 · Cited by 19
Pascual, G., Ricote, M., & Hevener, A. L. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.11.1503 · Cited by 12
O’Reilly, M. E., Ho, S., Coronel, J., Zhu, L., Liu, W., Xue, C., Kim, E., Cynn, E., Matias, C. V., Soni, R. K., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114240 · Cited by 7
Metadata
- Authors
- Vidal-Puig, A. J., Considine, R. V., Jimenez-Liñan, M., Werman, A., Pories, W. J., Caro, J. F., & Flier, J. S.
- Venue
- Journal of Clinical Investigation
- Published
- 1997-05-15
- Volume
- 99
- Issue
- 10
- Pages
- 2416-2422
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2089235913
- Cited by
- 786
- References
- 1
- FWCI
- 10.80
- Type
- journal article
- Language
- en
- Open access
- bronze
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