Gender differences in adiponectin modulation of cardiac remodeling in mice deficient in endothelial nitric oxide synthase

Jorge L. Durand, Andrea R. Nawrocki, Philipp E. Scherer, Linda A. Jelicks

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over-expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over-expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over-expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects.

Original languageEnglish (US)
Pages (from-to)3276-3287
Number of pages12
JournalJournal of Cellular Biochemistry
Volume113
Issue number10
DOIs
StatePublished - Oct 2012

Fingerprint

Nitric Oxide Synthase Type III
Adiponectin
Modulation
Left Ventricular Hypertrophy
High Fat Diet
Nutrition
Fats
Pathology
Magnetic resonance
Adipocytes
Sex Characteristics
Blood Vessels
Cause of Death
Anti-Inflammatory Agents
Cardiovascular Diseases

Keywords

  • Adiponectin
  • cardiac remodeling
  • eNOS
  • hypertension
  • left ventricular hypertrophy
  • MRI

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Gender differences in adiponectin modulation of cardiac remodeling in mice deficient in endothelial nitric oxide synthase. / Durand, Jorge L.; Nawrocki, Andrea R.; Scherer, Philipp E.; Jelicks, Linda A.

In: Journal of Cellular Biochemistry, Vol. 113, No. 10, 10.2012, p. 3276-3287.

Research output: Contribution to journalArticle

@article{87ec62486a1f48d0895f6dc1c476f12b,
title = "Gender differences in adiponectin modulation of cardiac remodeling in mice deficient in endothelial nitric oxide synthase",
abstract = "Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over-expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over-expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over-expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects.",
keywords = "Adiponectin, cardiac remodeling, eNOS, hypertension, left ventricular hypertrophy, MRI",
author = "Durand, {Jorge L.} and Nawrocki, {Andrea R.} and Scherer, {Philipp E.} and Jelicks, {Linda A.}",
year = "2012",
month = "10",
doi = "10.1002/jcb.24206",
language = "English (US)",
volume = "113",
pages = "3276--3287",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "10",

}

TY - JOUR

T1 - Gender differences in adiponectin modulation of cardiac remodeling in mice deficient in endothelial nitric oxide synthase

AU - Durand, Jorge L.

AU - Nawrocki, Andrea R.

AU - Scherer, Philipp E.

AU - Jelicks, Linda A.

PY - 2012/10

Y1 - 2012/10

N2 - Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over-expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over-expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over-expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects.

AB - Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over-expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over-expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over-expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects.

KW - Adiponectin

KW - cardiac remodeling

KW - eNOS

KW - hypertension

KW - left ventricular hypertrophy

KW - MRI

UR - http://www.scopus.com/inward/record.url?scp=84865006433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865006433&partnerID=8YFLogxK

U2 - 10.1002/jcb.24206

DO - 10.1002/jcb.24206

M3 - Article

VL - 113

SP - 3276

EP - 3287

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 10

ER -