PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance

Naoto Kubota, Yasuo Terauchi, Hiroshi Miki, Hiroyuki Tamemoto, Toshimasa Yamauchi, Kajuro Komeda, Shinobu Satoh, Ryosuke Nakano, Chikara Ishii, Takuya Sugiyama, Eto Kazuhiro, Yoshiharu Tsubamoto, Akira Okuno, Koji Murakami, Hisahiko Sekihara, Go Hasegawa, Makoto Naito, Yasushi Toyoshima, Satoshi Tanaka, Kunio ShiotaToshio Kitamura, Toshiro Fujita, Osamu Ezaki, Shinichi Aizawa, Ryozo Nagai, Kazuyuki Tobe, Satoshi Kimura, Takashi Kadowaki

Research output: Contribution to journalArticle

1133 Citations (Scopus)

Abstract

Agonist-induced activation of peroxisome proliferator-activated receptor γ (PPARγ) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPARγ was investigated by gene targeting. Homozygous PPARγ-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPARγ-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPARγ agonist treatment. Heterozygous PPARγ-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPARγ in high-fat-diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPARγ.

Original languageEnglish
Pages (from-to)597-609
Number of pages13
JournalMolecular Cell
Volume4
Issue number4
DOIs
Publication statusPublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology

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    Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Komeda, K., Satoh, S., Nakano, R., Ishii, C., Sugiyama, T., Kazuhiro, E., Tsubamoto, Y., Okuno, A., Murakami, K., Sekihara, H., Hasegawa, G., Naito, M., Toyoshima, Y., Tanaka, S., ... Kadowaki, T. (1999). PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Molecular Cell, 4(4), 597-609. https://doi.org/10.1016/S1097-2765(00)80210-5