健脾疏肝降脂方通过调节FGF21/PGC-1α/UCP1信号通路促进单纯性肥胖小鼠白色脂肪棕色化机制研究OA

Objective It is to explore the effect of Jianpi Shugan Jiangzhi Formula(JSJF)on simple obesity in mice via fibroblast growth factor 21(FGF21)/peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)/uncoupling pro-tein 1(UCP1).Methods Seventy-two male C57BL/6J mice were taken,12 of which were randomly selected as normal group,and the remaining mice were fed with high fat diet to establish models of obesity.The successfully modeled mice were randomly divided into model group,atorvastatin group,high-dose,medium-dose and low-dose groups of JSJF,with 12 mice in each group.The high-dose,medium-dose and low-dose groups of JSJF were given JSJF 26.52 g(crude drug)/kg,13.26 g(crude drug)/kg,6.63 g(crude drug)/kg via gastric lavage,respectively;the atorvastatin group was given 1.3 mg/kg atorvastatin solution via gastric lavage,while the control group and model group were given double-distilled water via gastric lavage,all once daily,continuously treated for 8 weeks.All groups received the solution once daily at a dose of 0.2 mL per administration for 8 weeks.After the final gavage,the body weights of mice in each group were measured,and the liver function markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST)]and blood lipid markers[total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)]were measured,the adipocyte morphology was observed by HE staining,and the positive expressions of FGF21,PGC-1α,peroxisome proliferator-activated receptor γ(PPARγ)and UCP1 in adipose tissue were detected by immunofluo-rescence,the mRNA and protein expressions of FGF21,PGC-1α,PPARγ,and UCP1 in adipose tissue were detected by Real-time PCR and Western blot,respectively.Results Compared with the control group,the body weight of mice in the model group was significantly increased(P<0.05),and the serum levels ofALT,AST,LDL-C,TC,and TG were all significantly increased(all P<0.05),while the serum level of HDL-C was significantly reduced(P<0.05);the adipo-cytes were irregularly arranged,and their diameters were significantly increased,the number of adipocytes per unit area was decreased;the fluorescence signal intensity and relative mRNA and protein expressions of FGF21,PGC-1α,PPARγ and UCP1 in adipose tissue(except for mRNA expression of PPARγ)were not significantly changed(all P>0.05).Compared with the control group,the body weights of mice in the high-dose group of JSJF and atorvastatin group were significantly lighter(all P<0.05),and the serum levels ofALT,AST,LDL-C,TC and TG were all significantly lower(all P<0.05);the adipocyte arrangement was slightly more regular,their diameters were decreased,and the numbers of adipo-cytes per unit area were increased;the fluorescence signal intensity and relative mRNA and protein expressions of FGF21,PGC-1α,PPARγ and UCP1 in adipose tissue were all significantly increased(all P<0.05);compared with the atorvasta-tin group,the fluorescence signal intensities of FGF21 and PPARγ,as well as relative mRNA and protein expressions of FGF21 and UCP1 in adipose tissue were significantly increased in the high-dose group of JSJF(all P<0.05).Conclusion JSJF can reduce body weight and improve lipid metabolism disorders of mice with simple obesity;its mechanism of action may be related to the regulation of the FGF21/PGC-1α/PPARγ/UCP1 signaling pathway in adipose tissue to promote the browning of white fat.