[PDF][PDF] PPARγ mediates high-fat diet–induced adipocyte hypertrophy and insulin resistance

N Kubota, Y Terauchi, H Miki, H Tamemoto… - Molecular cell, 1999 - cell.com
N Kubota, Y Terauchi, H Miki, H Tamemoto, T Yamauchi, K Komeda, S Satoh, R Nakano…
Molecular cell, 1999cell.com
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 …
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.
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