Methyl Brevifolincarboxylate 通过 AMPK/NF-κB 信号通路减弱肝细胞中游离脂肪酸诱导的脂质代谢和炎症,International Journal of Molecular Sciences

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Methyl Brevifolincarboxylate 通过 AMPK/NF-κB 信号通路减弱肝细胞中游离脂肪酸诱导的脂质代谢和炎症
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2021-09-17 , DOI: 10.3390/ijms221810062
Madamanchi Geethangili, Chiao-Wei Lin, Harry J. Mersmann, Shih-Torng Ding

非酒精性脂肪性肝病 (NAFLD) 的流行是全球慢性肝病的主要原因之一。这项研究检查了天然存在的多酚化合物短叶叶酸甲酯 (MBC) 对体外脂肪肝损伤的潜在保护作用。结果表明，非细胞毒性浓度的 MBC 降低了油酸 (OA) 处理的人肝癌细胞系、SK-HEP-1 和鼠原代肝细胞中的脂滴积累和甘油三酯 (TG) 水平。在 OA 处理的 SK-HEP-1 细胞和原代鼠肝细胞中，MBC 减弱了从头脂肪生成分子、乙酰辅酶 A 羧化酶 ( Acc1 )、脂肪酸合酶 ( Fasn ) 和甾醇调节元件结合蛋白 1c的 mRNA 表达水平(Srebp1c )。MBC在 SK-HEP-1 细胞和原代小鼠中促进脂质氧化因子过氧化物酶体增殖物激活受体-α ( Pparα ) 及其靶基因肉碱棕榈酰转移酶 1 ( Cpt1 ) 和酰基辅酶 A 氧化酶 1 ( Acox1 )肝细胞。OA 处理的 SK-HEP-1 细胞中脂肪生成和脂质氧化分子的蛋白表达减弱，进一步支持了 mRNA 结果。MBC 增加了 AMP 活化蛋白激酶 (AMPK) 磷酸化的表达。另一方面，MBC 治疗抑制了炎症介质、肿瘤坏死因子 ( TNF )-α、白细胞介素-6 ( IL-6 )、IL-8和IL-1β通过 OA 处理的 SK-HEP-1 细胞中活性氧的产生减少，分泌和核因子 (NF)-κB 表达（mRNA 和蛋白质）。总之，我们的结果表明，MBC 通过 AMPK/NF-κB 信号通路改善脂质代谢和炎症标志物，在体外对 NAFLD 具有潜在的保护作用。

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Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator’s, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1β secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway.

更新日期：2021-09-17

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