Obeticholic acid's effect on HDL function in MASH varies by diabetic status

IF 1.8 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Lipids Pub Date : 2024-07-16 DOI:10.1002/lipd.12408
Chunki Kim, Tsung-Heng Tsai, Rocio Lopez, Arthur McCullough, Takhar Kasumov
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Abstract

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro-inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid-lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro-inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre-β-HDL—the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA-induced change in pro-inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large-scale study.

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奥贝胆酸对 MASH 中高密度脂蛋白功能的影响因糖尿病状态而异。
炎症和氧化应激是代谢功能障碍相关性脂肪性肝炎(MASH)和动脉粥样硬化发病机制的关键因素。奥贝胆酸(OCA)是一种法尼类固醇 X 受体(FXR)激动剂,可改善 MASH 患者的肝脏炎症和纤维化。然而,它也会降低高密度脂蛋白胆固醇,这表明 OCA 可能会增加 MASH 患者患心血管疾病(CVD)的风险。我们对一小群有糖尿病和无糖尿病的患者(n = 10/组)在基线和接受 OCA 治疗 18 个月后的高密度脂蛋白胆固醇外流功能、抗氧化剂(副氧自由基酶和脑磷脂酶活性)、促炎症指数和颗粒大小进行了评估。服用降脂药物(他汀类药物、纤维素类药物)的患者除外。基线时,无糖尿病的 MASH 患者铁蛋白水平更高(336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL,p
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来源期刊
Lipids
Lipids 生物-生化与分子生物学
CiteScore
4.20
自引率
5.30%
发文量
33
审稿时长
4-8 weeks
期刊介绍: Lipids is a journal of the American Oil Chemists'' Society (AOCS) that focuses on publishing high-quality peer-reviewed papers and invited reviews in the general area of lipid research, including chemistry, biochemistry, clinical nutrition, and metabolism. In addition, Lipids publishes papers establishing novel methods for addressing research questions in the field of lipid research.
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