关键词: 山奈酚, 胰岛素受体, 过氧化物酶体增殖物激活受体γ, 肥胖, 脂肪积累

Abstract: Objective To explore the mechanism by which kaempferol inhibits adipose accumulation in obese rats through regulating the expression of insulin receptor(INSR)and peroxisome proliferator-activated receptor γ(PPARG). Methods Experimental rats were randomly divided into the following groups:Control,model,low-dose kaempferol,high-dose kaempferol,and betaine group.Except for the control group,all groups were subjected to obesity induction.The liver index,Lee's index,and the fat-to-body-weight ratio were calculated.Serum levels of lipid profiles(TC,TG,LDL-C,HDL-C),inflammatory factors(TNF-α,IL-6),and liver injury markers(AST,ALT),as well as fasting plasma glucose(FPG),and fasting insulin(FINS)were measured.The homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.Hematoxylin and eosin(HE)staining was performed to assess pathological changes in the liver and adipose tissues.Oil red O staining was used to evaluate hepatic lipid deposition.Immunohistochemistry was performed to detect the expression of CCAAT/enhancer binding protein α(C/EBPα)and acetyl-CoA carboxylase(ACC).Western blotting was used to determine INSR and PPARG protein expression.qRT-PCR was performed to quantify the mRNA levels of C/EBPα,ACC,INSR,and PPARG. Results Compared with the control group,adipocytes in the model group were significantly larger and exhibited marked hypertrophy and hyperplasia,with a disordered arrangement.In the liver tissue,hepatocytes showed extensive vacuolation,increased steatosis,and notable inflammatory cell infiltration;the number and size of lipid droplets were also markedly increased.Furthermore,the liver index,Lee's index,fat-to-body weight ratio,and serum levels of TC,TG,LDL-C,FPG,FINS,HOMA-IR,TNF-α,IL-6,AST,and ALT,were all significantly elevated(all P<0.05).Concurrently,the relative mRNA and protein levels of C/EBPα and ACC,as assessed by qRT-PCR and immunohistochemistry,respectively,were increased(all P<0.05).The relative mRNA and protein levels of PPARG were also upregulated,whereas HDL-C level and the relative mRNA and protein levels of INSR were significantly reduced(all P<0.05).Compared with the model group,the low-dose kaempferol,high-dose kaempferol,and betaine groups showed significant alleviation of pathological damage in adipose and liver tissues,with marked reductions in lipid droplets and lipid accumulation.All measured indices were significantly improved(all P<0.05). Conclusion Kaempferol attenuates adipose accumulation in obese rats,potentially by upregulating INSR expression and downregulating PPARG expression.

Key words: kaempferol, insulin receptor, PPARG, obesity, adipose accumulation