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Fagopyrum dibotrys extract improves nonalcoholic fatty liver disease via inhibition of lipogenesis and endoplasmic reticulum stress in high-fat diet-fed mice

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机构: [1]Kunming Med Univ, Affiliated Hosp 1, Yunnan Inst Digest Dis, Yunnan Clin Res Ctr Digest Dis, Kunming 650032, Yunnan, Peoples R China [2]Dali Univ, Dali Prefecture Peoples Hosp, Dept Gastroenterol, Affiliated Hosp 3, Dali 671003, Yunnan, Peoples R China [3]Kunming Med Univ, Inst Biomed Engn, Yunnan Key Lab Stem Cell & Regenerat Med, Kunming 650500, Yunnan, Peoples R China
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关键词: Nonalcoholic fatty liver disease Fagopyrum dibotrys extract High-fat diet Endoplasmic reticulum stress Lipid metabolism

摘要:
Objective The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, presenting a treatment challenge due to limited options. Endoplasmic reticulum (ER) stress and associated lipid metabolism disorders are main causes of NAFLD, making it important to inhibit ER stress for effective treatment. Fagopyrum dibotrys has hypolipidemic, anti-inflammatory and hepatoprotective properties, showing promise in treating NAFLD. However, its effects on ER stress in NAFLD remain unclear. This study used a high-fat diet (HFD) to establish NAFLD mouse models and supplemented with Fagopyrum dibotrys extract (FDE) to evaluate its therapeutic effect and underlying mechanisms. Results We showed that FDE supplementation reduced the severity of hepatic steatosis and lowered triglycerides (TG) and total cholesterol (TC) levels in NAFLD mice. At the molecular level, FDE supplementation reduced hepatic lipid deposition by downregulating lipogenic markers (SREBP-1c, SCD1) and upregulating fatty acid oxidase CPT1 alpha expression. Additionally, FDE treatment inhibited the overexpression of ER stress markers (GRP78, CHOP, and P-EIF2 alpha) in NAFLD mice livers, and blocked the activation of the PERK-EIF2 alpha-CHOP pathway, demonstrating its role in maintaining ER homeostasis. Considering that activation of the PERK pathway could exacerbate lipid deposition, our findings suggest that FDE has a protective effect against hepatic steatosis in NAFLD mice by attenuating ER stress, and the potential mechanism is through inhibiting the PERK pathway.

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Q2 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Kunming Med Univ, Affiliated Hosp 1, Yunnan Inst Digest Dis, Yunnan Clin Res Ctr Digest Dis, Kunming 650032, Yunnan, Peoples R China
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