Decreased expression of natriuretic peptides associated with lipid accumulation in cardiac ventricle of obese mice.
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 (α- and β-myosin heavy chain and α-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.
Bartels
Emil Daniel
ED
Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Nielsen
Jan Møller
JM
Bisgaard
Line Stattau
LS
Goetze
Jens P
JP
Nielsen
Lars Bo
LB
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism*
D011498:Protein Precursors; D012333:RNA, Messenger; D014280:Triglycerides; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor