Leptin Improves Fatty Liver Independently of Insulin Sensitization and Appetite Suppression in Hepatocyte-Specific Pten-Deficient Mice with Insulin Hypersensitivity
| Autor: | Megumi Aizawa-Abe, Sachiko Yamamoto-Kataoka, Mingming Zhao, Daisuke Aotani, Kazuwa Nakao, Miki Nishio, Kiminori Hosoda, Akira Suzuki, Chihiro Ebihara, Takeru Sakai, Yuji Yamamoto, Toru Kusakabe, Valentino Gumbilai, Ken Ebihara |
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| Rok vydání: | 2014 |
| Předmět: |
Leptin
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Appetite AMP-Activated Protein Kinases Biology Biochemistry Mice Endocrinology Insulin resistance Non-alcoholic Fatty Liver Disease Internal medicine Nonalcoholic fatty liver disease medicine Animals Humans Insulin Triglycerides Mice Knockout Leptin receptor digestive oral and skin physiology Biochemistry (medical) Fatty liver PTEN Phosphohydrolase General Medicine medicine.disease Liver Hepatocytes Metabolic syndrome Lipodystrophy |
| Zdroj: | Hormone and Metabolic Research. 47:168-175 |
| ISSN: | 1439-4286 0018-5043 |
| DOI: | 10.1055/s-0034-1395531 |
| Popis: | Nonalcoholic fatty liver disease (NAFLD) is recognized as the hepatic component of the metabolic syndrome. Although NAFLD is a major cause of cirrhosis and cancer of the liver of unknown cause, no established pharmacological treatment for NAFLD has been established yet. It has been reported that leptin treatment improved fatty liver dramatically as well as insulin resistance and hyperphagia in patients with lipodystrophy. However, it is unclear whether leptin improves fatty liver independently of these metabolic improvements. We investigated the liver effect of leptin independently of insulin sensitization and appetite suppression using hepatocyte-specific Pten-deficient (AlbCrePtenff) mouse, a model of severe fatty liver with insulin hypersensitivity. Male AlbCrePtenff mice were infused subcutaneously with leptin (20 ng/g/h) for 2 weeks using osmotic minipumps. Leptin infusion effectively reduced liver weight, liver triglyceride content, and glutamate pyruvate transaminase (GPT) concentrations as well as food intake and body weight without the change of plasma insulin concentration in AlbCrePtenff mice. Pair-feeding also reduced body weight but not liver triglyceride content. Pair feeding reduced α1 and α2 AMP-activated protein kinase (AMPK) activities and PGC1α gene expression in the liver, while leptin infusion unchanged them. The present study clearly demonstrated that leptin improve fatty liver independently of insulin sensitization and suppression of food intake. It was suggested that leptin improves fatty liver by stimulation of β-oxidation in the liver. The present study might provide a further understanding on the mechanism of metabolic effect of leptin. |
| Databáze: | OpenAIRE |
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