The Mechanisms by Which Both Heterozygous Peroxisome Proliferator-activated Receptor γ (PPARγ) Deficiency and PPARγ Agonist Improve Insulin Resistance
Autor: | Toshimasa Yamauchi, Naoto Kubota, Ryozo Nagai, Kajuro Komeda, Yasuo Terauchi, Kazuyuki Tobe, Yasuo Akanuma, Satoshi Kimura, Junji Kamon, Koji Murakami, Hiroshi Miki, Tomohiro Ide, Takashi Kadowaki, Atsuko Tsuchida, Hironori Waki, Kiyoto Motojima |
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Rok vydání: | 2001 |
Předmět: |
Heterozygote
medicine.medical_specialty Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor White adipose tissue Biology Biochemistry Mice chemistry.chemical_compound Insulin resistance Downregulation and upregulation Internal medicine Adipocyte Adipocytes medicine Animals Insulin Obesity Molecular Biology Triglycerides chemistry.chemical_classification Adiponectin Muscles Cell Biology medicine.disease Up-Regulation Thiazoles Endocrinology Liver chemistry Lipogenesis Insulin Resistance Adipocyte hypertrophy Signal Transduction Transcription Factors |
Zdroj: | Journal of Biological Chemistry. 276:41245-41254 |
ISSN: | 0021-9258 |
Popis: | Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated transcription factor and a member of the nuclear hormone receptor superfamily that is thought to be the master regulator of fat storage; however, the relationship between PPARgamma and insulin sensitivity is highly controversial. We show here that supraphysiological activation of PPARgamma by PPARgamma agonist thiazolidinediones (TZD) markedly increases triglyceride (TG) content of white adipose tissue (WAT), thereby decreasing TG content of liver and muscle, leading to amelioration of insulin resistance at the expense of obesity. Moderate reduction of PPARgamma activity by heterozygous PPARgamma deficiency decreases TG content of WAT, skeletal muscle, and liver due to increased leptin expression and increase in fatty acid combustion and decrease in lipogenesis, thereby ameliorating high fat diet-induced obesity and insulin resistance. Moreover, although heterozygous PPARgamma deficiency and TZD have opposite effects on total WAT mass, heterozygous PPARgamma deficiency decreases lipogenesis in WAT, whereas TZD stimulate adipocyte differentiation and apoptosis, thereby both preventing adipocyte hypertrophy, which is associated with alleviation of insulin resistance presumably due to decreases in free fatty acids, and tumor necrosis factor alpha, and up-regulation of adiponectin, at least in part. We conclude that, although by different mechanisms, both heterozygous PPARgamma deficiency and PPARgamma agonist improve insulin resistance, which is associated with decreased TG content of muscle/liver and prevention of adipocyte hypertrophy. |
Databáze: | OpenAIRE |
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