title: PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.
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 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.
authors.affiliation: Department of Metabolic Diseases, University of Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kubota
authors.forename: Y
authors.initials: Y
authors.lastname: Terauchi
authors.forename: H
authors.initials: H
authors.lastname: Miki
authors.forename: H
authors.initials: H
authors.lastname: Tamemoto
authors.forename: T
authors.initials: T
authors.lastname: Yamauchi
authors.forename: K
authors.initials: K
authors.lastname: Komeda
authors.forename: S
authors.initials: S
authors.lastname: Satoh
authors.forename: R
authors.initials: R
authors.lastname: Nakano
authors.forename: C
authors.initials: C
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: K
authors.initials: K
authors.lastname: Eto
authors.forename: Y
authors.initials: Y
authors.lastname: Tsubamoto
authors.forename: A
authors.initials: A
authors.lastname: Okuno
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: H
authors.initials: H
authors.lastname: Sekihara
authors.forename: G
authors.initials: G
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.forename: Y
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Shiota
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: O
authors.initials: O
authors.lastname: Ezaki
authors.forename: S
authors.initials: S
authors.lastname: Aizawa
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D048429:Cell Size / Q000235:genetics*; D004032:Diet; D004435:Eating; D004734:Energy Metabolism; D005223:Fats / Q000494:pharmacology*; D005328:Fetal Viability / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D020738:Leptin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D000077205:Pioglitazone; D010920:Placenta / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D005223:Fats; D007004:Hypoglycemic Agents; D020738:Leptin; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077205:Pioglitazone