title: Pathophysiogical role of leptin in lifestyle-related diseases. Studies with transgenic skinny mice overexpressing leptin.
abstract: Leptin is a major adipocyte-derived hormone that is involved in the regulation of food intake and energy expenditure. Plasma leptin concentrations are elevated in obese subjects, suggesting its pathophysiological role in obesity-related lifestyle-related diseases. We have recently succeeded in the generation of transgenic skinny mice overexpressing leptin. They exhibit increased glucose metabolism and insulin sensitivity accompanied by a significant increase in insulin signaling for glucose utilization in the skeletal muscle and liver. They also show blood pressure elevation through the sympathetic activation. Introduction of the lethal yellow agouti (A(y)) allele into transgenic skinny mice results in late-onset obesity and diabetes with blood pressure elevation similar to those found in nontransgenic agouti mice (A(y)/+ mice). After caloric restriction, blood pressure elevation is reversed but insulin resistance still remains in A(y)/+ mice in parallel with a reduction of plasma leptin concentrations. By contrast, blood pressure elevation is sustained but insulin resistance is reversed in transgenic mice overexpressing leptin with the A(y) allele (Tg/+:A(y)/+ mice), which remain hyperleptinemic. Collectively, our data suggest the pathophysiologic and therapeutic implication of leptin in obesity-related insulin resistance and hypertension.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin, Kawahara-cho, Sakyo-ku, 606-8507, Kyoto, Japan. ogawa@kuhp-kyoto-u.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Shintani
authors.forename: Megumi
authors.initials: M
authors.lastname: Aizawa-Abe
authors.forename: Fumiko
authors.initials: F
authors.lastname: Miyanaga
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D004038:Diet, Reducing; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000235:genetics* / Q000502:physiology*; D008019:Life Style; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D020738:Leptin; D005947:Glucose