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

1115 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

Fingerprint

Peroxisome Proliferator-Activated Receptors
High Fat Diet
Adipocytes
Hypertrophy
Insulin Resistance
Phenotype
Gene Targeting
Leptin
Embryonic Structures
Obesity
Fats
Alleles

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Komeda, K., ... 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

PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. / Kubota, Naoto; Terauchi, Yasuo; Miki, Hiroshi; Tamemoto, Hiroyuki; Yamauchi, Toshimasa; Komeda, Kajuro; Satoh, Shinobu; Nakano, Ryosuke; Ishii, Chikara; Sugiyama, Takuya; Kazuhiro, Eto; Tsubamoto, Yoshiharu; Okuno, Akira; Murakami, Koji; Sekihara, Hisahiko; Hasegawa, Go; Naito, Makoto; Toyoshima, Yasushi; Tanaka, Satoshi; Shiota, Kunio; Kitamura, Toshio; Fujita, Toshiro; Ezaki, Osamu; Aizawa, Shinichi; Nagai, Ryozo; Tobe, Kazuyuki; Kimura, Satoshi; Kadowaki, Takashi.

In: Molecular Cell, Vol. 4, No. 4, 1999, p. 597-609.

Research output: Contribution to journalArticle

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, Shiota, K, Kitamura, T, Fujita, T, Ezaki, O, Aizawa, S, Nagai, R, Tobe, K, Kimura, S & Kadowaki, T 1999, 'PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance', Molecular Cell, vol. 4, no. 4, pp. 597-609. https://doi.org/10.1016/S1097-2765(00)80210-5
Kubota, Naoto ; Terauchi, Yasuo ; Miki, Hiroshi ; Tamemoto, Hiroyuki ; Yamauchi, Toshimasa ; Komeda, Kajuro ; Satoh, Shinobu ; Nakano, Ryosuke ; Ishii, Chikara ; Sugiyama, Takuya ; Kazuhiro, Eto ; Tsubamoto, Yoshiharu ; Okuno, Akira ; Murakami, Koji ; Sekihara, Hisahiko ; Hasegawa, Go ; Naito, Makoto ; Toyoshima, Yasushi ; Tanaka, Satoshi ; Shiota, Kunio ; Kitamura, Toshio ; Fujita, Toshiro ; Ezaki, Osamu ; Aizawa, Shinichi ; Nagai, Ryozo ; Tobe, Kazuyuki ; Kimura, Satoshi ; Kadowaki, Takashi. / PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. In: Molecular Cell. 1999 ; Vol. 4, No. 4. pp. 597-609.
@article{bbaecc28871b4b6f8c6b3f1b00cfabdb,
title = "PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance",
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.",
author = "Naoto Kubota and Yasuo Terauchi and Hiroshi Miki and Hiroyuki Tamemoto and Toshimasa Yamauchi and Kajuro Komeda and Shinobu Satoh and Ryosuke Nakano and Chikara Ishii and Takuya Sugiyama and Eto Kazuhiro and Yoshiharu Tsubamoto and Akira Okuno and Koji Murakami and Hisahiko Sekihara and Go Hasegawa and Makoto Naito and Yasushi Toyoshima and Satoshi Tanaka and Kunio Shiota and Toshio Kitamura and Toshiro Fujita and Osamu Ezaki and Shinichi Aizawa and Ryozo Nagai and Kazuyuki Tobe and Satoshi Kimura and Takashi Kadowaki",
year = "1999",
doi = "10.1016/S1097-2765(00)80210-5",
language = "English",
volume = "4",
pages = "597--609",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance

AU - Kubota, Naoto

AU - Terauchi, Yasuo

AU - Miki, Hiroshi

AU - Tamemoto, Hiroyuki

AU - Yamauchi, Toshimasa

AU - Komeda, Kajuro

AU - Satoh, Shinobu

AU - Nakano, Ryosuke

AU - Ishii, Chikara

AU - Sugiyama, Takuya

AU - Kazuhiro, Eto

AU - Tsubamoto, Yoshiharu

AU - Okuno, Akira

AU - Murakami, Koji

AU - Sekihara, Hisahiko

AU - Hasegawa, Go

AU - Naito, Makoto

AU - Toyoshima, Yasushi

AU - Tanaka, Satoshi

AU - Shiota, Kunio

AU - Kitamura, Toshio

AU - Fujita, Toshiro

AU - Ezaki, Osamu

AU - Aizawa, Shinichi

AU - Nagai, Ryozo

AU - Tobe, Kazuyuki

AU - Kimura, Satoshi

AU - Kadowaki, Takashi

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033212964&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033212964&partnerID=8YFLogxK

U2 - 10.1016/S1097-2765(00)80210-5

DO - 10.1016/S1097-2765(00)80210-5

M3 - Article

C2 - 10549291

AN - SCOPUS:0033212964

VL - 4

SP - 597

EP - 609

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 4

ER -