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PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.

Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-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 PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.

Pubmed ID: 10549291


  • 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
  • Kadowaki T


Molecular cell

Publication Data

October 26, 1999

Associated Grants


Mesh Terms

  • Adipocytes
  • Animals
  • Blood Glucose
  • Body Weight
  • Cell Differentiation
  • Cell Size
  • Diet
  • Eating
  • Energy Metabolism
  • Fats
  • Fetal Viability
  • Hypoglycemic Agents
  • Insulin Resistance
  • Leptin
  • Mice
  • Mice, Knockout
  • Myocardium
  • Placenta
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors