The Effects Of Osteocalcin Intermittent Injections On The Prevention Of High Fat Diet-Induced Nonalcoholic Fatty Liver Disease In Mice

Objective Osteocalcin is an osteoblast-specific secreted protein that, when undercarboxylated, which is a serum marker reflecting bone transformation and also behaves as a hormone regulating glucose metabolism and fat mass. Recently,circulating markers of bone metabolism, including osteocalcin, which might be the active regulator in a bone-liver axis, have been found to be altered in patients with NAFLD. Our study is to investigate the effects of exogenous osteocalcin intermittent injections on the high fat diet-induced model of nonalcoholic fatty liver disease(NAFLD) in wild type mice.Methods Five-week-old C57Bl/6J male mice were randomly divided into four groups:(1) Normal Diet;(2) High Fat Diet + Vehicle;(3) High Fat Diet +Osteocalcin3 ng·g-1·d-1;(4) High Fat Diet +Osteocalcin 10 ng·g-1·d-1. We monitored body weight,fasting blood glucose, glucose tolerance and food intake during the 24 weeks’ study.Serum total cholesterol(TC), triglyceride(TG), free fatty acid(FFA), tumor necrosis factor α(TNF-α) and liver TC, liver TG were measured at the end of the study. We also stained livers with Oil Red O and Hematoxylin-Eosin.Results(1) Compared with high fat diet group, total fat mass in groups of osteocalcin treatment significantly decreased(P<0.001). Fat beside epididymis and around kidneys as well as subcutaneous fat and total fat mass/body mass ratio reduced in mice treated with both 3 ng·g-1·d-1 and 10 ng·g-1·d-1 of osteocalcin(P<0.001). Micein groups with daily injections osteocalcin with 3 ng·g-1·d-1 and 10 ng·g-1·d-1 have lower fasting blood glucose and improved glucose tolerance(P<0.05~0.001). Serum levels of TC, TG, FFA and TNF-α were also significantly decreased in the groups treated by different doses of osteocalcin(P<0.05);(2)Two different doses of osteocalcin daily injection could prevent high fat diet-induced liver steatosis. Liver weight and ratio of liver weight to body weight as well as liver contents of TC and TG were significantly decreased in mice treated with 3 ng·g-1·d-1 and 10 ng·g-1·d-1 of osteocalcin(P<0.05).Conclusion Daily injections of osteocalcin in two different doses both can significantly prevent high fat diet-induced NAFLD, improve glucose-lipid metabolism and reduce serum TNF-α level.