PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.
Journal:
Mol. Cell 1999 OctAuthors:
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
Abstract
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 ph
...[more]enotypes 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.[less]
Mesh Headings:
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