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Climate, Food Systems, Diet, Nutrition and Health (Poster Session)

(P23-027-25) A Low-Fat Diet Intervention Altered DNA Methylation of KCNQ1 Gene in Adipose Tissue Rather Than Liver of Nonalcoholic Steatohepatitis

Monday, June 2, 2025
12:45 PM - 1:45 PM ET
Location: Poster Board C-26

    Presenting Author(s)

  • Na Wu

    Post doctor
    State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, School of Public Health
    Shanghai, Shanghai, China (People's Republic)

    • Co-Author(s)

  • GJ

    Guang Ji

    State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, China (People's Republic)

Disclosure(s):
Na Wu: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: This study aimed to investigate the role of DNA methylation of KCNQ in nonalcoholic steatohepatitis (NASH) after diet intervention.

Methods: Male C57BL/6 mice (n = 38) with specific pathogen-free grades at 9 weeks of age were used in this study. The mice were randomly assigned to either a methionine choline-deficient diet (MCD, n = 23) or a methionine choline sufficient diet (MCS, n = 15) group, respectively, and were fed for 4 weeks. After 4 weeks, 7 mice in each group were sacrificed to check whether they were NASH mice. Then NASH mice were randomly assigned to 2 groups for a 4-week intervention period: feeding with a low-fat diet (LFD, n = 8) and an MCD diet (n = 8). The control group remained on the MCS diet (n = 8). MethylRAD was used to quantify the methylation of genomic DNA from the liver and adipose tissue in these NASH mice. EpiTYPER and quantitative real-time polymerase chain reaction were used to quantify DNA methylation and mRNA expression of KCNQ1 in NASH mice after LFD intervention.

Results: Following LFD intervention, staining revealed decreased vesicular degeneration. Body weight, and weight of liver and epididymal fat pad, cholesterol, and triglyceride levels were much higher in the LFD group than in the MCD group (p < 0.05), while serum alanine amino-transferase and aspartate amino-transferase decreased significantly after LFD intervention (p < 0.01). Hyper-methylation in the intron of KCNQ1 was observed after LFD intervention in the liver and adipose tissue of NASH mice (p < 0.05) with methylRAD sequencing. High DNA methylation and low mRNA expression of KCNQ1 were validated in adipose of NASH mice in response to LFD (p  < 0.05 with EpiTYPER array.

Conclusions: The study reinforced the role of DNA methylation in regulating gene expression of KCNQ1 in response to LFD intervention and highlighted the DNA methylation of KCNQ1 in NASH adipose tissue could be tissue-specific. All these results contribute to elucidating the molecular mechanisms underlying the activities of DNA methylation in NASH.

Funding Sources: This work was supported by Shanghai 2023 “Science and Technology Innovation Action Plan” Qi Ming Xing Cultivation (Yang Fan Project, 23YF1447700) and the National Natural Science Foundation of China (82405047).