Decreased expression of natriuretic peptides associated with lipid accumulation in cardiac ventricle of obese mice
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Decreased expression of natriuretic peptides associated with lipid accumulation in cardiac ventricle of obese mice. / Bartels, E.D.; Nielsen, J.M.; Bisgaard, L.S.; Goetze, J.P.; Nielsen, L.B.; Nielsen, Lars Bo.
In: Endocrinology, Vol. 151, No. 11, 01.11.2010, p. 5218-25.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Decreased expression of natriuretic peptides associated with lipid accumulation in cardiac ventricle of obese mice
AU - Bartels, E.D.
AU - Nielsen, J.M.
AU - Bisgaard, L.S.
AU - Goetze, J.P.
AU - Nielsen, L.B.
AU - Nielsen, Lars Bo
PY - 2010/11/1
Y1 - 2010/11/1
N2 - Plasma B-type natriuretic peptide (BNP) and proBNP are established markers of cardiac dysfunction. Even though obesity increases the risk of cardiovascular disease, obese individuals have reduced plasma concentrations of natriuretic peptides. The underlying mechanism is not established. We used cultured cardiomyocytes and three different mouse models to examine the impact of obesity and cardiac lipid accumulation on cardiac natriuretic peptide expression. The cardiac ventricular expression of atrial natriuretic peptide (ANP) and BNP mRNA and ANP peptide was decreased 36-72% in obese ob/ob, db/db, and fat-fed C57BL/6 mice as compared with their respective controls. The db/db and ob/ob mice displayed impaired cardiac function, whereas the fat-fed mice had almost normal cardiac function. Moreover, the ventricular expression of hypertrophic genes (a- and ß-myosin heavy chain and a-actin) and natriuretic peptide receptor genes were not consistently altered by obesity across the three mouse models. In contrast, cardiac ventricular triglycerides were similarly increased by 60-115% in all three obese mouse models and incubation with oleic acid caused triglyceride accumulation and an approximately 35% (P <0.005) depression of ANP mRNA expression in cultured HL-1 atrial myocytes. The data suggest that obesity and altered cardiac lipid metabolism are associated with reduced production of ANP and BNP in the cardiac ventricles in the setting of normal as well as impaired cardiac function.
AB - Plasma B-type natriuretic peptide (BNP) and proBNP are established markers of cardiac dysfunction. Even though obesity increases the risk of cardiovascular disease, obese individuals have reduced plasma concentrations of natriuretic peptides. The underlying mechanism is not established. We used cultured cardiomyocytes and three different mouse models to examine the impact of obesity and cardiac lipid accumulation on cardiac natriuretic peptide expression. The cardiac ventricular expression of atrial natriuretic peptide (ANP) and BNP mRNA and ANP peptide was decreased 36-72% in obese ob/ob, db/db, and fat-fed C57BL/6 mice as compared with their respective controls. The db/db and ob/ob mice displayed impaired cardiac function, whereas the fat-fed mice had almost normal cardiac function. Moreover, the ventricular expression of hypertrophic genes (a- and ß-myosin heavy chain and a-actin) and natriuretic peptide receptor genes were not consistently altered by obesity across the three mouse models. In contrast, cardiac ventricular triglycerides were similarly increased by 60-115% in all three obese mouse models and incubation with oleic acid caused triglyceride accumulation and an approximately 35% (P <0.005) depression of ANP mRNA expression in cultured HL-1 atrial myocytes. The data suggest that obesity and altered cardiac lipid metabolism are associated with reduced production of ANP and BNP in the cardiac ventricles in the setting of normal as well as impaired cardiac function.
KW - Animals
KW - Atrial Natriuretic Factor
KW - Cells, Cultured
KW - Heart Ventricles
KW - Mice
KW - Myocytes, Cardiac
KW - Natriuretic Peptide, Brain
KW - Obesity
KW - Protein Precursors
KW - RNA, Messenger
KW - Random Allocation
KW - Statistics, Nonparametric
KW - Triglycerides
U2 - 10.1210/en.2010-0355
DO - 10.1210/en.2010-0355
M3 - Journal article
C2 - 20844006
VL - 151
SP - 5218
EP - 5225
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0013-7227
IS - 11
ER -
ID: 33815100