Lingguizhugan Decoction(LGZG)has been investigated in basic studies,with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease(NAFLD).This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting.A randomized,double-blinded,placebo-controlled trial was performed.A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG(two groups:standard dose and low dose)or placebo for 12 weeks on the basis of lifestyle modifications.The primary efficacy variable was homeostasis model assessment of insulin resistance(HOMA-IR).Analyses were performed in two populations in accordance with body mass index(BMI;overweight/obese,BMI≥24 kg/m2;lean,BMI＜24 kg/m2).For overweight/obese participants,low-dose LGZG significantly decreased their HOMA-IR level compared with placebo(-0.19(1.47)versus 0.08(1.99),P=0.038).For lean subjects,neither dose of LGZG showed a superior effect compared with placebo.Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A(PPP1R3A)and autophagy related 3(ATG3)significantly increased after LGZG intervention in overweight/obese population.Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD.The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3.Lean subjects may not be a targeted population for LGZG.

Liang Dai;Jingjuan Xu;Baocheng Liu;Yanqi Dang;Ruirui Wang;Lijie Zhuang;Dong Li;Lulu Jiao;Jianying Wang;Lei Zhang;Linda L.D.Zhong;Wenjun Zhou;Guang Ji

Institute of Digestive Diseases,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Clinical Research Academy,Peking University Shenzhen Hospital,Shenzhen 518032,China;Department of Integrated Traditional and Western Medicine,Jinling Hospital,Medical School of Nanjing University,Nanjing 210002,China;Shanghai Innovation Centre of TCM Health Service,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Sanlin Health Centre of Pudong New District,Shanghai 200120,China;Zhangjiang Health Centre of Pudong New District,Shanghai 201203,China;Beicai Health Centre of Pudong New District,Shanghai 201204,China;Hong Kong Chinese Medicine Study Centre,Hong Kong Baptist University,Hong Kong 999077,China

医学前沿

[1]Liang Dai;Jingjuan Xu;Baocheng Liu;Yanqi Dang;Ruirui Wang;Lijie Zhuang;Dong Li;Lulu Jiao;Jianying Wang;Lei Zhang;Linda L.D.Zhong;Wenjun Zhou;Guang Ji-.Lingguizhugan Decoction,a Chinese herbal formula,improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease:a translational approach)[J].医学前沿,2022(05):745-759

Lingguizhugan,LGZG,PPP1R3A

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