Obesity-induced upregulation of myocardial endothelin-1 expression is mediated by leptin.
Several studies have shown that leptin, the product of the obese gene, may link obesity with cardiovascular diseases, and in particular with cardiac hypertrophy. In vitro studies suggest that the mechanism by which leptin causes cardiac hypertrophy involves the upregulation of endogenous endothelin-1 (ET-1), a potent vasoconstrictor and mitogen. Whether obesity-associated hyperleptinemia causes an increase in myocardial ET-1 expression in vivo remains unclear. To address this issue, we fed mice with a high-fat diet and analyzed serum levels of ET-1 and ET-1 mRNA in the heart. We found that in mice fed a high-fat diet, serum ET-1, myocardial ET-1, leptin and leptin receptor mRNA were all elevated. In contrast, in leptin-deficient obese (ob/ob) mice, both serum and myocardial ET-1 levels were not higher than in wild type mice. These findings suggest that upregulation of myocardial ET-1 by obesity is mediated by leptin.
Adiarto
Suko
S
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Emoto
Noriaki
N
Iwasa
Naoko
N
Yokoyama
Mitsuhiro
M
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis; D004041:Dietary Fats / Q000008:administration & dosage; D019332:Endothelin-1 / Q000096:biosynthesis*; D000072396:Endothelin-Converting Enzymes; D020738:Leptin / Q000502:physiology*; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis; D051379:Mice; D008820:Mice, Obese; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000503:physiopathology*; D015854:Up-Regulation
D004041:Dietary Fats; D019332:Endothelin-1; D020738:Leptin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes