Improvement Of Insulin Sensitivity By Osteocalcin Inhibits Inflammation In The Adipose Tissue Of Obese Mice

Obesity is a serious health problem that increases the risk for various metabolic disorders,such as cardiovascular disease,hypertension,hyperlipidemia and type 2 diabetes and is linked to chronic,low-grade systemic inflammatory response.Adipose tissue macrophages(ATMs)play an important role in obesity-associated inflammation and insulin resistance.However,macrophage chemotaxis protein-1(MCP-1)is one of the important factors that causes the incursion of macrophages in adipose tissue.Many studies are committed to exploring an effective method to reduce the inflammation of adipose tissue,improving insulin resistance and preventing the development of type 2 diabetes.Osteocalin,as a special protein secreted from osteoblasts,early studies discover that it plays an important role in bone formation and bone transformation.However,osteocalin has recently received attention as a circulating hormone implicated in the regulation of glucose and energy metabolism.we have futher explored the different doses of osteocalcin in blood glucose,body fat mass,insulin level and inflammation in adipose tissue and related mechanisms,to further enlarge the research field of osteocalcin and make a new progress in reducing obesity related inflammatory response.Following C57 BL / 6 mice were fed with high fat diet for 12 weeks,obese mice were obtained and injected with osteocalcin(30ng/kg or 3 ng/kg)and saline solution(control)by ip for other 4 weeks.Fat mass,body weight,serum triglycerides,free fatty acid,fasting blood glucose were analyzed.Insulin tolerance test were carried out.Macrophages infiltration degree in adipose tissue were observed by immunohistochemical stain.The expression of macrophage chemotaxis protein(MCP-1)and CD68 mRNA were detected by real-time fluorescent quantitative PCR.According to the experimental result,Osteocalcin(30ng/kg or 3ng/kg)treatment for 4 weeks can significantly reduced the body weight,fat mass,the levels of fasting plasma glucose and insulin level in obese mice.Moreover,macrophage infiltration decreased,and the expression of MCP-1 and CD68 mRNA were down-regulated in adipose tissue of obese mice treated with osteocalcin(30ng/kg).There were pimelitis and insulin resistance in rat obesity induced by high calorie and high-fat diet.Osteocalin can inhibit the infiltration of macrophages and expression of MCP-1 and then attenuate the inflammation and improve insulin resistance in rats.Osteocalcin(30ng/kg)can significantly reduces body weight,fat mass and improves severity of insulin resistance through down-regulated expression of MCP-1 and CD68 mRNA and inbibition of macrophage infiltration in adipose tissue of obese mice induced by high fat diet.