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Sci. STKE, 2 November 1999
Vol. 1999, Issue 6, p. tw1
[DOI: 10.1126/stke.1999.6.tw1]


Regulation by PPAR{gamma} Regulation by PPAR{gamma}: Expanding its Biological Functions

The peroxisome proliferator-activated receptor (PPAR) family is comprised of ligand-regulated transcription factors that have been implicated in controlling lipid metabolism. When stimulated, PPAR{gamma} induces the expression of genes that mediate fatty acid uptake, metabolism, and storage. PPAR{gamma} activation also induces adipocyte differentiation and sensitivity to insulin. Barrak et al. and Kubota et al. have now generated PPAR{gamma}-deficient mice. Both groups show that PPAR{gamma}-deficient mice die during prenatal development due to a defect in placenta vacularization and heart development. Those mutant mice that survived following a placental reconstitution procedure displayed no adipose tissue and died shortly after birth. Heterozygote mutant mice did not exhibit adipocyte hypertrophy from a high fat diet nor did they show insulin resistance, indicating that both PPAR{gamma} alleles are required for obesity and insulin resistance to occur as the result of such a diet. Rosen et al. generated chimeric mice by injecting ES cells homozygous for PPAR{gamma} deficiency into wild type blastocysts, and also found that the gene was necessary for normal development of adipocytes. The expanse in PPAR{gamma} function revealed in these studies and the proposed and molecular control of these various processes by PPAR{gamma} are further discussed by Lowell.

Lowell, B.B. (1999) PPAR{gamma}: An essential regulator of adipogenesis and modulator of fat cell function. Cell 99: 239-242. [Online Journal]

Barak,Y., Nelson, M.C., Ong, E.S., Jones,Y.Z.,Ruiz-Lozano, P., Chien, K.R., Koder, A., and Evans, R.A. (1999) PPAR{gamma} is required for placental, cardiac, and adipose tissue development. Mol. Cell 4: 585-595. [Online Journal]

Kubota, N., Terauchi,Y., Miki, H., Tamemoto, H., Yamauchi, T., Komeda, K., Satoh, S., Nakano, R., Ishii, C., Sugiyama, T., Eto, K., Tsubamoto, Y., Okuno, A., Murakami, K., Sekihara, H., Hasegawa, G., Naito, M., Toyoshima, Y., Tanaka, S., Shiota, K., Kitamura, T., Fujita, T., Ezaki, O., Aizawa, S., Nagai, R., Tobe, K., Kimura, S., and Kadowaki, T. (1999) PPAR{gamma} mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol. Cell 4: 597-609. [Online Journal]

Rosen, E.D., Sarraf, P., Troy, A.E., Bradwin, G., Moore, K., Milstone, D.S., Spiegelman, B.M., and Mortensen, R.M. (1999) PPAR{gamma} is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4: 611-617. [Online Journal]

Citation: Regulation by PPAR{gamma}: Expanding its Biological Functions. Sci. STKE 1999, tw1 (1999).

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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882