Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach
1. Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China 2. Clinical Research Academy, Peking University Shenzhen Hospital, Shenzhen 518032, China 3. Department of Integrated Traditional and Western Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China 4. Shanghai Innovation Centre of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China 5. Sanlin Health Centre of Pudong New District, Shanghai 200120, China 6. Zhangjiang Health Centre of Pudong New District, Shanghai 201203, China 7. Beicai Health Centre of Pudong New District, Shanghai 201204, China 8. Hong Kong Chinese Medicine Study Centre, Hong Kong Baptist University, Hong Kong 999077, China
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/m 2). 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.
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