GH-independent IGF-I action is essential to prevent the development of nonalcoholic steatohepatitis in a GH-deficient rat model.
The progression to nonalcoholic steatohepatitis (NASH) from simple steatosis is associated with the mitochondrial dysfunction, enhanced oxidative stress, and inflammation. Recently, it has been reported that the prevalence of NAFLD (nonalcoholic fatty liver disease)/NASH is increased in patients with adult growth hormone deficiency (AGHD), suggesting that the deficiencies in GH and insulin-like growth factor (IGF-I) are involved in the development of NAFLD/NASH; however, the precise underlying mechanism remains to be elucidated. To clarify the mechanisms and the specific contribution of GH and IGF-I in these conditions, we examined the liver of a GH-deficient rat model, spontaneous dwarf rat (SDR) and the effect of GH and IGF-I administration. SDR showed steatosis and fibrosis in the liver in line with the phenotype observed in AGHD. Serum AST and ALT levels and triglyceride content in the liver were significantly increased in the SDR compared with the control. Intriguingly, the mitochondrial morphology in the SDR hepatocyte was impaired and the area was significantly decreased. Furthermore, oxidative stress in the SDR liver was enhanced. These changes were improved not only by GH but also by IGF-I administration, suggesting that GH-independent IGF-I action plays an essential role in the liver. In conclusion, we demonstrated that GH-deficient rat exhibits NASH and IGF-I plays an essential role to prevent the development of NASH. The improved mitochondrial function and reduced oxidative stress may contribute the effect of IGF-I in the liver.
Department of Internal Medicine, Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.
Hitoshi
H
Nishizawa
Michiko
M
Takahashi
Hidenori
H
Fukuoka
Genzo
G
Iguchi
Riko
R
Kitazawa
Yutaka
Y
Takahashi
D000818:Animals; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000473:pathology / Q000517:prevention & control*; D013006:Growth Hormone / Q000008:administration & dosage / Q000172:deficiency*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D008930:Mitochondria, Liver / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone