Cardiac lipid accumulation associated with diastolic dysfunction in obese mice

Christina Christoffersen; Entela Bollano; Marie L S Lindegaard; Emil D Bartels; Jens P Goetze; Claus B Andersen; Lars B Nielsen

doi:10.1210/en.2003-0242

Cardiac lipid accumulation associated with diastolic dysfunction in obese mice

Christina Christoffersen, Entela Bollano, Marie L S Lindegaard, Emil D Bartels, Jens P Goetze, Claus B Andersen, Lars B Nielsen

266 Citations (Scopus)

Abstract

Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.

Original language	English
Journal	Molecular Endocrinology
Volume	144
Issue number	8
Pages (from-to)	3483-90
Number of pages	8
ISSN	0013-7227
DOIs	https://doi.org/10.1210/en.2003-0242
Publication status	Published - Aug 2003

Keywords

Animals
Apolipoproteins B/genetics
Carrier Proteins/genetics
Collagen/analysis
Diastole/physiology
Echocardiography
Fatty Acid Transport Proteins
Fatty Acids/metabolism
Gene Expression
Leptin/deficiency
Lipid Metabolism
Lipoprotein Lipase/genetics
Membrane Proteins/genetics
Membrane Transport Proteins
Mice
Mice, Knockout
Mice, Obese
Microscopy, Electron
Mitochondria, Heart/metabolism
Myocardium/chemistry
Natriuretic Peptide, Brain/genetics
Obesity/physiopathology
Oxidation-Reduction
Phosphatidylcholines/analysis
Phosphatidylinositols/analysis
RNA, Messenger/analysis
Systole/physiology
Triglycerides/analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1210/en.2003-0242

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title = "Cardiac lipid accumulation associated with diastolic dysfunction in obese mice",

abstract = "Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.",

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author = "Christina Christoffersen and Entela Bollano and Lindegaard, {Marie L S} and Bartels, {Emil D} and Goetze, {Jens P} and Andersen, {Claus B} and Nielsen, {Lars B}",

year = "2003",

month = aug,

doi = "10.1210/en.2003-0242",

language = "English",

volume = "144",

pages = "3483--90",

journal = "Molecular Endocrinology",

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TY - JOUR

T1 - Cardiac lipid accumulation associated with diastolic dysfunction in obese mice

AU - Christoffersen, Christina

AU - Bollano, Entela

AU - Lindegaard, Marie L S

AU - Bartels, Emil D

AU - Goetze, Jens P

AU - Andersen, Claus B

AU - Nielsen, Lars B

PY - 2003/8

Y1 - 2003/8

N2 - Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.

AB - Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.

KW - Animals

KW - Apolipoproteins B/genetics

KW - Carrier Proteins/genetics

KW - Collagen/analysis

KW - Diastole/physiology

KW - Echocardiography

KW - Fatty Acid Transport Proteins

KW - Fatty Acids/metabolism

KW - Gene Expression

KW - Leptin/deficiency

KW - Lipid Metabolism

KW - Lipoprotein Lipase/genetics

KW - Membrane Proteins/genetics

KW - Membrane Transport Proteins

KW - Mice

KW - Mice, Knockout

KW - Mice, Obese

KW - Microscopy, Electron

KW - Mitochondria, Heart/metabolism

KW - Myocardium/chemistry

KW - Natriuretic Peptide, Brain/genetics

KW - Obesity/physiopathology

KW - Oxidation-Reduction

KW - Phosphatidylcholines/analysis

KW - Phosphatidylinositols/analysis

KW - RNA, Messenger/analysis

KW - Systole/physiology

KW - Triglycerides/analysis

U2 - 10.1210/en.2003-0242

DO - 10.1210/en.2003-0242

M3 - Journal article

C2 - 12865329

SN - 0888-8809

VL - 144

SP - 3483

EP - 3490

JO - Molecular Endocrinology

JF - Molecular Endocrinology

IS - 8

ER -

Cardiac lipid accumulation associated with diastolic dysfunction in obese mice

Abstract

Keywords

UN SDGs

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