Sci. STKE, 2 November 1999
Regulation by PPAR Regulation by PPAR: 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 induces the expression of genes that mediate fatty acid uptake, metabolism, and storage. PPAR activation also induces adipocyte differentiation and sensitivity to insulin. Barrak et al. and Kubota et al. have now generated PPAR-deficient mice. Both groups show that PPAR-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 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 deficiency into wild type blastocysts, and also found that the gene was necessary for normal development of adipocytes. The expanse in PPAR function revealed in these studies and the proposed and molecular control of these various processes by PPAR are further discussed by Lowell.
Lowell, B.B. (1999) PPAR: 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 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 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 is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4: 611-617. [Online Journal]
Citation: Regulation by PPAR: Expanding its Biological Functions. Sci. STKE 1999, tw1 (1999).
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