Study On Electroacupuncture Regulates White Adipose Tissue Browning By Promoting SIRT-1-Dependent PPAR γ Deacetylation And Mitochondrial Biogenesis

Background:Electroacupuncture(EA)can inducing white adipose tissue(WAT)browning to counter obesity had been reported by previous studies.But the underlying molecular mechanism was still not very clear.Aim:To study the molecular mechanism of WAT browning by EA,basing on the Based on the regulation of sirtuin typel(SIRT-1)dependent peroxisome proliferator-activated receptor γ(PPAR γ)deacetylation on browning genes,like uncoupling protein 1(UCP1).And the more scientific experimental basis for the clinical application on EA countering obesity would be shown in this study.Method:1.Both the normal diet group(ND)and high-fat diet(HFD)group were composed of three-week-old SD rats.10 weeks after modeling,the HFD rats were regrouped into the HFD control group and the HFD+EA group.Body weight and cumulative food intake were monitored every week;2.The HFD+EA group were electro-acupunctured for 4 weeks on Tianshu(ST25)acupoint under gas anesthesia with isoflurane,while the ones in HFD group were under gas anesthesia only.We selected continuous-wave stimulation at a frequency of 2/15 Hz(intensity 2mA),and six time every week,a total of 4 weeks.Body weight and cumulative food intake were monitored every week in order to study the effect of EA combating obesity on obese rats;3.H&E staining was performed to assess adipocyte size.The effect of EA on WAT was assessed by qPCR,immunoblotting,immunoprecipitation and Co-immunoprecipitation.Mitochondria was isolated from IWAT to observe the expression of mitochondrial transcription factor A(TFAM).Results:EA decreased the body weight,WAT/body weight ratio,the WAT adipocyte area and cumulative food consumption obviously(P<0.05)of the obese rats.As well as the mRNA expressions of WAT genes Nevertheless,the mRNA expressions of brown adipose tissue(BAT)markers were increased a 4-week EA treatment.Moreover,the protein expressions of SIRT-1,PPAR y,PPAR y coactivator 1α(PGC-1α),UCP1 and PR domain containing 16(PRDM16)which trigger the molecular conversion of WAT browning was upregulated by EA.The acetylation of PPAR γ was downregulated in the EA group,indicating EA could promote WAT-browning through SIRT-1 dependent PPAR γ deacetylation pathway.Besides,it was found that EA could activate AMP-activated protein kinase(AMPK)to further regulate PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis.Conclusion:In brief,EA can remodel WAT to BAT through inducing SIRT-1 dependent PPAR y deacetylation,and regulating PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis.This may be one of the mechanisms by which EA affects weight loss.