S100A16 Influence On Glucolipid Metabolism And Its Molecular Mechanism

S100A16 protein encoded by the S100A16 gene in humans is a newly identified EF-hand Ca2+-binding protein that facilitates adipogenesis.Rats aged 8 weeks were randomly divided into normal diet group(NF,n = 10)and a high-fat diet group(HF,n = 10),providing diet for 16 weeks to establish a diet induced obesity(DIO)rat model.When feeding at 14 weeks,rats were processed intraperitoneal glucose tolerance test(IPGTT)and insulin release test(IRT).When rats were executed after 16 weeks,weighted subcutaneous and visceral fat weight.Then we used HE staining method(hematoxylin and eosin staining,HE)to observe the liver steatosis degree,radiation immunity analysis to check blood sugar,insulin,serum uric acid,serum biochemical indicator,and Western blotting to study the expression of S100A16 and glucolipid metabolism related protein expression of transcription factors in liver and adipose tissue.The result is DIO group rats weight and visceral fat is significantly higher than normal group.The serum total cholesterol and uric acid in DIO group was higher than normal glucose tolerance and insulin release is lower than the normal group.Western blotting showed that in liver and fat tissue of DIO group,S100A16,PPAR-y,C/EPB-a expression were significantly higher than those of normal group.By using transgenic mice models,this study is designed to give a examination of the role of S100A16 in energy metabolism related to diet-induced obesity.Unexpectedly we found that abnormal glucose metabolism in dietary induced obesity is not caused by weight gain but overexpression of S100A16.In one hand,S100A16 can promote the lipogenesis in result to lipid drops gather in fat cells rather than into the blood stream by interact with cyclinA,cyclinE,CDK2,P53.In the other hand,S100A16 negatively impacts insulin sensitivity through combined with P53 indirectly.Thus,High fat diet can increase the expression of S100A16 and related expression of transcription factors;S100A16 over expression can promote lipid generated and result in a negative impact on insulin release and insulin sensitivity.Inhibition of adipose tissue S100A16 prevents obesity-associated hyperlipidaemia in mice,but also causes glucose regulation weakness,which suggests that diet-induced S100A16 expression in adipose tissue represents a selective advantage for Hyperlipidemia patients,but this effect compromises glycometabolism.