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Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach.

Abstract
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.
AuthorsLiang 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
JournalFrontiers of medicine (Front Med) Vol. 16 Issue 5 Pg. 745-759 (Oct 2022) ISSN: 2095-0225 [Electronic] China
PMID35471471 (Publication Type: Randomized Controlled Trial, Journal Article)
Copyright© 2022. Higher Education Press.
Chemical References
  • DNA
Topics
  • Humans
  • Non-alcoholic Fatty Liver Disease (complications, drug therapy)
  • Overweight (complications, drug therapy)
  • Insulin Resistance
  • Obesity (complications, drug therapy)
  • China
  • DNA (therapeutic use)

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