The Effects Of Irisin On Lipolysis And Autocrine Function In Adipocytes And Its Relationships With Bone Mineral Density And Body Composition In POCS Patients

Irisin, which was identified as a myokine and an adipokine in 2012 and closely associated with obesity and related metabolic diseases, made the “browning” of white adipose tissue and has increasingly caught the attention of the medical and scientific community. Although research has shown that irisin could increase the expression of UCP1 in adipocyte and promote the differentiation of osteoblast in vitro, the signaling pathway of irisin and the molecular mechanisms responsible for the lipolysis effect remain unclear. Moreover, the autocrine of irisin in fat cells was not studied. In addition, Polycystic ovary syndrome was an endocrine disease that associated with obesity, and its pathogenesis was still unclear. It was not clear whether irisin associated with the body composition in PCOS patients. Based on this background, we carried out the basic and clinical research.Firstly, we established an efficient system for the expression and purification of GST-irisin in Escherichia coli. The biological activity of GST-irisin was verified using the cell counting kit-8 assay and by detecting the m RNA expression of uncoupling protein 1. Our data showed that GST-irisin regulates mRNA levels of lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase and proteins such as the fatty acid-binding protein 4, leading to increased secretion of glycerol and decreased lipid accumulation in 3T3-L1 adipocytes. In addition, exogenous GST-irisin can increase its autocrine function in vitro by regulating the expression of fibronectin type III domain-containing protein 5.GST-irisin could regulate glucose uptake in 3T3-L1 adipocytes. Hence, we believe that recombinant GST-irisin could promote lipolysis and its secretion in vitro and can potentially prevent obesity and related metabolic diseases.Secondly, fifty two PCOS and 39 control women were recruited. Serum sex hormone, fasting insulin and C-peptide were tested. Fasting serum irisin and adiponectin were measured with enzyme-linked immunosorbent assay. Body composition and bone mineral density were assayed by dual energy X-rayabsorptiometry. Our data showed that polycystic ovary syndrome women showed different body compositions compared with controls. Serum irisin level of PCOS did not show significant difference compared with controls although it was decreased. The level of adiponectin in PCOS patients was significantly reduced.BMI had no correlation with irisin level. It indicated a positive correlation between serum irisin levels and bone mineral density in the control group and a negative correlation in the PCOS group after BMI and age adjusted. Furthermore, total lean mass has a significant effect on irisin concentration in the PCOS group. There are no correlations between adiponection and body compositions and bone mineral density in both groups. Hence, we believe that the abnormal body composition in PCOS may contribute to the circulation irisin. The crosstalk of irisin in different organs was found and may be related to disease development in PCOS.