Pathophysiogical role of leptin in lifestyle-related diseases: Studies with transgenic skinny mice overexpressing leptin

Yoshihiro Ogawa, Hiroaki Masuzaki, Ken Ebihara, Mitsuyo Shintani, Megumi Aizawa-Abe, Fumiko Miyanaga, Kazuwa Nakao

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 (Ay) allele into transgenic skinny mice results in late-onset obesity and diabetes with blood pressure elevation similar to those found in nontransgenic agouti mice (Ay/+ mice). After caloric restriction, blood pressure elevation is reversed but insulin resistance still remains in Ay/+ 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 Ay allele (Tg/+:Ay/+ mice), which remain hyperleptinemic. Collectively, our data suggest the pathophysiologic and therapeutic implication of leptin in obesity-related insulin resistance and hypertension.

Original languageEnglish
Pages (from-to)119-122
Number of pages4
JournalJournal of Diabetes and Its Complications
Volume16
Issue number1
DOIs
Publication statusPublished - Mar 5 2002
Externally publishedYes

Fingerprint

Leptin
Transgenic Mice
Life Style
Insulin Resistance
Blood Pressure
Obesity
Alleles
Appetite Regulation
Glucose
Caloric Restriction
Adipocytes
Energy Metabolism
Skeletal Muscle
Hormones
Insulin
Hypertension
Liver

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Pathophysiogical role of leptin in lifestyle-related diseases : Studies with transgenic skinny mice overexpressing leptin. / Ogawa, Yoshihiro; Masuzaki, Hiroaki; Ebihara, Ken; Shintani, Mitsuyo; Aizawa-Abe, Megumi; Miyanaga, Fumiko; Nakao, Kazuwa.

In: Journal of Diabetes and Its Complications, Vol. 16, No. 1, 05.03.2002, p. 119-122.

Research output: Contribution to journalArticle

Ogawa, Yoshihiro ; Masuzaki, Hiroaki ; Ebihara, Ken ; Shintani, Mitsuyo ; Aizawa-Abe, Megumi ; Miyanaga, Fumiko ; Nakao, Kazuwa. / Pathophysiogical role of leptin in lifestyle-related diseases : Studies with transgenic skinny mice overexpressing leptin. In: Journal of Diabetes and Its Complications. 2002 ; Vol. 16, No. 1. pp. 119-122.
@article{e177e39f90504d319cd214ca2caaa0ae,
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 (Ay) allele into transgenic skinny mice results in late-onset obesity and diabetes with blood pressure elevation similar to those found in nontransgenic agouti mice (Ay/+ mice). After caloric restriction, blood pressure elevation is reversed but insulin resistance still remains in Ay/+ 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 Ay allele (Tg/+:Ay/+ mice), which remain hyperleptinemic. Collectively, our data suggest the pathophysiologic and therapeutic implication of leptin in obesity-related insulin resistance and hypertension.",
author = "Yoshihiro Ogawa and Hiroaki Masuzaki and Ken Ebihara and Mitsuyo Shintani and Megumi Aizawa-Abe and Fumiko Miyanaga and Kazuwa Nakao",
year = "2002",
month = "3",
day = "5",
doi = "10.1016/S1056-8727(01)00204-5",
language = "English",
volume = "16",
pages = "119--122",
journal = "Journal of Diabetes and its Complications",
issn = "1056-8727",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Pathophysiogical role of leptin in lifestyle-related diseases

T2 - Studies with transgenic skinny mice overexpressing leptin

AU - Ogawa, Yoshihiro

AU - Masuzaki, Hiroaki

AU - Ebihara, Ken

AU - Shintani, Mitsuyo

AU - Aizawa-Abe, Megumi

AU - Miyanaga, Fumiko

AU - Nakao, Kazuwa

PY - 2002/3/5

Y1 - 2002/3/5

N2 - 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 (Ay) allele into transgenic skinny mice results in late-onset obesity and diabetes with blood pressure elevation similar to those found in nontransgenic agouti mice (Ay/+ mice). After caloric restriction, blood pressure elevation is reversed but insulin resistance still remains in Ay/+ 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 Ay allele (Tg/+:Ay/+ mice), which remain hyperleptinemic. Collectively, our data suggest the pathophysiologic and therapeutic implication of leptin in obesity-related insulin resistance and hypertension.

AB - 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 (Ay) allele into transgenic skinny mice results in late-onset obesity and diabetes with blood pressure elevation similar to those found in nontransgenic agouti mice (Ay/+ mice). After caloric restriction, blood pressure elevation is reversed but insulin resistance still remains in Ay/+ 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 Ay allele (Tg/+:Ay/+ mice), which remain hyperleptinemic. Collectively, our data suggest the pathophysiologic and therapeutic implication of leptin in obesity-related insulin resistance and hypertension.

UR - http://www.scopus.com/inward/record.url?scp=0036180430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036180430&partnerID=8YFLogxK

U2 - 10.1016/S1056-8727(01)00204-5

DO - 10.1016/S1056-8727(01)00204-5

M3 - Article

C2 - 11872379

AN - SCOPUS:0036180430

VL - 16

SP - 119

EP - 122

JO - Journal of Diabetes and its Complications

JF - Journal of Diabetes and its Complications

SN - 1056-8727

IS - 1

ER -