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• W2291382005 abstract "Leptin, an adipocyte-derived hormone, plays crucial roles in the regulation of energy expenditure and food intake. Through analyses of leptin transgenic mice, we have demonstrated that leptin has pleiotropic effects such as regulation of insulin sensitivity and lipid metabolism. Lipodystrophy is a disease characterized by a lack of adipose tissue, which leads to metabolic disorders including insulin resistant diabetes, hypertriglyceridemia, and fatty liver. We demonstrated that leptin deficiency plays an important role in the pathogenesis of metabolic disorders in lipodystrophy. We also demonstrated the efficacy of leptin replacement therapy in lipodystrophy. Leptin improves insulin sensitivity at least partly by cancellation of lipotoxicity in the liver and skeletal muscle. It is also possible that leptin improves insulin secretion by cancellation of lipotoxicity in pancreatic beta cells. Using animal models, we demonstrated that leptin activates hepatic AMP-activated protein kinase (AMPK), and hepatic AMPK activation is involved in the therapeutic effects of leptin. To elucidate the pathogenic mechanism of hyperphagia in lipodystrophy, we measured food-related neural activity by fMRI and investigated subjective feelings of appetite. We found insufficiency of postprandial suppression of food-related neural activity and formation of satiety feelings in patients with lipodystrophy, which might be largely due to leptin deficiency. In March 2013, marketing and manufacturing approval was granted for metreleptin for the treatment of lipodystrophy in Japan on the basis of the results of our investigator-initiated trial. This is the first global approval of leptin formulation. Leptin has potential as a drug for the treatment of more common metabolic diseases including diabetes, hyperlipidemia, and fatty liver." @default.
• W2291382005 created "2016-06-24" @default.
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• W2291382005 date "2015-01-01" @default.
• W2291382005 modified "2023-09-26" @default.
• W2291382005 title "Translational Research of Leptin in Lipodystrophy and Its Related Diseases" @default.
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• W2291382005 doi "https://doi.org/10.1007/978-4-431-55651-0_14" @default.
• W2291382005 hasPublicationYear "2015" @default.
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