Impaired expression of cardiac adiponectin in leptin-deficient mice with viral myocarditis.
A mouse model of encephalomyocarditis (EMC) virus-induced myocarditis was used to investigate the expression of adiponectin in damaged cardiomyocytes. We intraperitoneally injected EMC virus into leptin-deficient ob/ob (OB) mice and wild-type (WT) mice. OB mice were divided into two subgroups consisting of mice with no intervention and mice receiving leptin replacement starting simultaneously with viral inoculation. We determined differences in heart weight, cardiac histological score, numbers of infiltrating and apoptotic cells in the myocardium, expression levels of adiponectin and TNF-alpha mRNA in the heart, adiponectin immunoreactivity in myocytes, adiponectin and TNF-alpha concentrations in the heart, and immunoreactivity of adiponectin receptors in myocytes between OB mice and WT mice. There was significantly decreased adiponectin mRNA expression, immunoreactivity, and protein level in the heart, and reduced immunoreactivity of adiponectin receptor 1 in myocytes from OB mice on days 4 and 8 after viral inoculation as compared with those in WT mice, together with increased cardiac weight, severe inflammatory myocardial damage, and increased levels of cardiac TNF-alpha mRNA and protein. Replacement of leptin in OB mice inhibited the development of severe myocarditis through augmentation of adiponectin mRNA, immunoreactivity, and protein level, increased adiponectin receptor 1 immunoreactivity in myocytes, and suppressed levels of TNF-alpha mRNA and protein. These results suggest that impaired expression of cardiac adiponectin may contribute to the progression of viral myocarditis through enhanced expression of TNF-alpha under a leptin-deficient condition.
Department of General Medicine, Kanazawa Medical University, Ishikawa, Japan.
Takashi
T
Takahashi
Fei
F
Yu
Seiichiro
S
Saegusa
Hiroyuki
H
Sumino
Takeshi
T
Nakahashi
Kunimitsu
K
Iwai
Shigeto
S
Morimoto
Masahiko
M
Kurabayashi
Tsugiyasu
T
Kanda
D052242:Adiponectin / Q000096:biosynthesis; D000818:Animals; D018188:Cardiovirus Infections / Q000150:complications; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus; D005260:Female; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000378:metabolism* / Q000821:virology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D052242:Adiponectin; C499919:Adipoq protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha