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Title: Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

Abstract

Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE; National Institutes of Health Grant HL059483 (US)
OSTI Identifier:
841312
Report Number(s):
LBNL-54224
R&D Project: 862U1A; TRN: US200513%%609
DOE Contract Number:  
AC03-76SF00098
Resource Type:
Journal Article
Journal Name:
Circulation
Additional Journal Information:
Journal Volume: 110; Other Information: Submitted to Circulation: Volume 110; Journal Publication Date: 11/16/2004; PBD: 1 Sep 2003
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ADIPOSE TISSUE; ARTERIOSCLEROSIS; BLOOD PRESSURE; DAILY VARIATIONS; DIET; GENES; GLUCOSE; HYPERTENSION; INDUCTION; INFLAMMATION; INSULIN; LEPTIN; LIPIDS; METABOLIC DISEASES; METABOLISM; MICE; PATHOGENESIS

Citation Formats

Verreth, Wim, Verhamme, Peter, Pelat, Michael, Ganame, Javier, Bielicki, John K., Mertens, Ann, Quarck, Rozenn, Benhabiles, Nora, Marguerie, Gerard, Mackness, Bharti, Mackness, Mike, Ninio, Ewa, Herregods, Marie-Christine, Balligand, Jean-Luc, and Holvoet, Paul. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice. United States: N. p., 2003. Web.
Verreth, Wim, Verhamme, Peter, Pelat, Michael, Ganame, Javier, Bielicki, John K., Mertens, Ann, Quarck, Rozenn, Benhabiles, Nora, Marguerie, Gerard, Mackness, Bharti, Mackness, Mike, Ninio, Ewa, Herregods, Marie-Christine, Balligand, Jean-Luc, & Holvoet, Paul. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice. United States.
Verreth, Wim, Verhamme, Peter, Pelat, Michael, Ganame, Javier, Bielicki, John K., Mertens, Ann, Quarck, Rozenn, Benhabiles, Nora, Marguerie, Gerard, Mackness, Bharti, Mackness, Mike, Ninio, Ewa, Herregods, Marie-Christine, Balligand, Jean-Luc, and Holvoet, Paul. Mon . "Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice". United States. https://www.osti.gov/servlets/purl/841312.
@article{osti_841312,
title = {Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice},
author = {Verreth, Wim and Verhamme, Peter and Pelat, Michael and Ganame, Javier and Bielicki, John K. and Mertens, Ann and Quarck, Rozenn and Benhabiles, Nora and Marguerie, Gerard and Mackness, Bharti and Mackness, Mike and Ninio, Ewa and Herregods, Marie-Christine and Balligand, Jean-Luc and Holvoet, Paul},
abstractNote = {Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.},
doi = {},
journal = {Circulation},
number = ,
volume = 110,
place = {United States},
year = {2003},
month = {9}
}