Leptin deficiency enhances myocardial necrosis and lethality in a murine model of viral myocarditis.
To investigate the role of leptin in the development of viral myocarditis and cardiac necrosis, we used a murine model of viral myocarditis. We intraperitoneally injected encephalomyocarditis virus (500 plaque-forming units/mouse) for wild type C57 BL/6 mice (WT) and leptin-deficient ob/ob mice (OB) (n = 20 for each). Ten-day survival rate was 25% in OB, whereas it was 95% in WT. Heart weights on day 10 were significantly elevated in OB compared with those in WT (107.2 +/- 9.4 vs. 96.6 +/- 7.9 mg, n = 4 for each). Thymus weights were significantly diminished in OB compared with those in WT on days 6 and 10. Histological score (grade 1 to 4 according to the size of involved area) for myocardial necrosis were significantly higher in OB than in WT (1.5 +/- 0.5 vs. 0.8 +/- 0.5, n = 4 for each). On day 4, viral titer in hearts was significantly elevated in OB compared with that in WT (3.3 +/- 0.5 vs. 1.9 +/- 0.2 TCID50/mg, n = 3 for each). Comparative expression of TNF-alpha mRNA in hearts from OB were significantly increased compared with those in WT on day 7 (n = 3 for each). Natural killer cell activities in spleens from OB were significantly lower than from WT on day 4 (27 +/- 5 vs. 42 +/- 8%, n = 4 for each). Thus, leptin deficiency could enhance severity of myocardial necrosis and mortality due to viral myocarditis.
Kanda
Tsugiyasu
T
Department of General Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan. kandat@kanazawa-med.ac.jp
Takahashi
Takashi
T
Kudo
Sumiyo
S
Takeda
Takeshi
T
Tsugawa
Hiroichi
H
Takekoshi
Noboru
N
D000818:Animals; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus; D006321:Heart / Q000821:virology; D006652:Histological Techniques; D007694:Killer Cells, Natural / Q000276:immunology; D020738:Leptin / Q000172:deficiency*; D051379:Mice; D008817:Mice, Mutant Strains; D009205:Myocarditis / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013950:Thymus Gland / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020738:Leptin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha