Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats.
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH) could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms.


RESULTS
High-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha) levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin), which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways.


CONCLUSIONS
Chronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance.
Qin
Ying
Y
Department of Clinical Biochemistry, Chinese People's Liberation Army General Hospital, 28 Fu-Xing Road, Beijing, China. qinying301@yahoo.com.cn
Tian
Ya-ping
YP
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D019382:Human Growth Hormone / Q000097:blood / Q000235:genetics* / Q000627:therapeutic use*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D052243:Resistin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D054411:Receptors, Leptin; D052243:Resistin; C499622:Retn protein, rat; D014409:Tumor Necrosis Factor-alpha; C506573:adiponectin receptor 2, rat; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I