Effects of irisin on lipid in mice and glycolipid metabolism in obese mice induced by diet

Abstract

Objective: To explore the role of low-dose irisin in the browning of white adipose tissue (WAT) and activation of brown adipose tissue (BAT) in mice, and its effect on the metabolic function of diet induced obesity. Methods: A total of 22 C57/BLKS/J male mice fed with normal diet and 8 fed with high fat diet were separately divided into experimental and control group. The experimental group was given irisin (0.8 ng/g, 200 μl), while the control group was given the same volume (200 μl) of phosphate buffer saline every day for 14 consecutive days intraperitoneally. Food intake and body weight of mice were collected regularly every day. After intervention, the mice were killed and the changes of lipid content and activity in adipose tissue were detected by histopathology and immunohistochemistry. The effects of irisin at different concentrations (0, 20 and 40 nmol/L) on primary white adipocytes and brown adipocytes were evaluated by immunohistochemistry on uncoupling protein 1(UCP1). In order to further evaluate whether irisin has the function of improving metabolism, the changes of serum indexes and hepatic steatosis in mice fed with high-fat diet were monitored. Results: The primary white and brown adipocytes derived from mice were successfully cultured and identified in vitro. In NCD mice, the weight gain of mice with irisin was lower than that of control mice [(-0.78±0.98) vs (0.27±0.55) g]. Histopathology showed that the area of white adipocytes with irisin was smaller than controls [(14.78±8.44) vs (29.49±12.97) μm2] and the brown adipocytes were larger than controls [(0.92±0.35) vs (0.19±0.12) μm2] (both P<0.05), while the expression of UCP1 in both adipose tissues was significantly higher in irisin group. After irisin treatment, the levels of blood glucose [(7.18±0.41) vs (13.48±2.07) mmol/L, P<0.01]and cholesterol [(2.38±0.26) vs (3.89±0.93) mmol/L, P<0.05] were significantly lower than controls, and the content of lipid droplets in liver cells was less than controls [ (2.73±1.96)% vs (14.04±6.29) %, P<0.001]. Conclusions: Low dose irisin can promote the browning of WAT and activate BAT, reducing the body weight of mice by producing heat. Irisin can also effectively improve diet-induced obesity and related metabolic disorders in mice.