Effect Of ARB On Expression Of NF-kB And PPARγ In Adipose Tissue Of Rats On Long-term High-fat-diet

ObjectiveTo observe the change of NF-kB and PPARγexpressions in adipose tissue of rats on long-term high-fat-diet and the effect of blockade the renin–angiotensin system (RAS) on it.MethodsThirty male rats were randomly divided into 3 groups: normal control (NC group, n=10), high-caloric and high-fat diet fed (HF group, n=10) and valsartan intervened (HV group, n=10), Three groups were fed with normal diet, high fat diet and high fat plus valsartan lavage respectively. Then the change of insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp, observing the change of adipocyte size in three groups with HE staining, the proteins of NF-kB and PPARγwere detected by immunohistochemistry, mRNA expressions of NF-kB and PPARγof adipose tissue were assayed with reverse transcription polymerase chain reaction.ResultsCompared with the NC group, glucose infusion rate in HF group was reduced significantly, the body weight, the ratio of epididymal fat weight to body weight and the fasting serum levels of insulin, triglyceride, free fat acids (FFAs) were significantly higher than those in the control (P<0.01), the rats in group HF shown insulin resistance (P<0.01). the mean area of adipocyte shown to be significantly larger by 5.2 folds(P<0.01) and adipocyte morphous was irregular in group HF, the protein and the mRNA expressions of NF-kB in the epididymal fat tissue were all increased by 1.8 folds and 1.62 folds, respectively(all P<0.01), the protein and the mRNA expressions of PPARγwere all increased by 1.4 folds and 1.26 folds, respectively(all P<0.01).The HV group intervened by valsartan (40mg*kg-1*d-1) for 8 weeks, Compared with the HF group, the ratio of epidimal fat weight to body weight decreased significantly (P<0.01), the insulin sensitivity in HV group was higher, the area of adipocyte shown to be decreased by 59% (P<0.01), the protein and the mRNA expressions of NF-kB were decreased by 21% and by 31% (all P<0.01). PPARγwas activated, the protein and mRNA expressions of PPARγwas higher by 28% and by 19% (all P<0.01).ConclusionInsulin resistance rats could be induced by long-term high-fat-diet, in which adipocyte hypertrophy, the expressions of nuclear factor NF-kB and PPARγwere increased in adipose tissue. AngiotensinⅡreceptor blocker (ARB) drugs valsartan can decrease the expression of inflammatory factor NF-kB, activate PPARγ, modulate the adipocyte shape, which may be one of the mechanisms involved in the improvement of obesity-induced inflammation and insulin resistance.