γ-Linolenic Acid Prevents Lipid Metabolism Disorder in Palmitic Acid-Treated Alpha Mouse Liver-12 Cells by Balancing Autophagy and Apoptosis via the LKB1-AMPK-mTOR Pathway,Journal of Agricultural and Food Chemistry

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γ-Linolenic Acid Prevents Lipid Metabolism Disorder in Palmitic Acid-Treated Alpha Mouse Liver-12 Cells by Balancing Autophagy and Apoptosis via the LKB1-AMPK-mTOR Pathway
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2021-07-19 , DOI: 10.1021/acs.jafc.1c02596
Yaxu Liang ₁ , Zhen Zhang ₁ , Jiayu Tu ₁ , Zhibo Wang ₁ , Xiaoxiao Gao ₁ , Kaiping Deng ₁ , M A El-Samahy ₁ , Peihua You ₂ , Yixuan Fan ₁ , Feng Wang ₁

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Excessive fat deposition is the main character in nonalcoholic fatty liver disease (NAFLD), while γ-linolenic acid (GLA) is a polyunsaturated fatty acid that can reduce lipid deposition. This study investigated the effect and regulatory mechanism of GLA (100 μM) on lipid metabolism in alpha mouse liver 12 (AML-12) cells treated by 400 μM palmitic acid (PA). GLA reduced lipid content and increased fatty acid β oxidation, as indicated by decreasing triglyceride and cholesterol contents and increasing mRNA and protein expressions of CPT1α and PPARα. GLA relieved oxidative stress caused by PA, upregulated mRNA levels of superoxide dismutase and glutathione peroxidase, and decreased reactive oxygen species content. GLA reduced apoptosis, as indicated by decreases in the BAX/BCL2 expression level and apoptosis percentage. GLA activated autophagy, autophagosome-lysosome fusion, and LKB1-AMPK-mTOR signaling and upregulated mRNA and protein expressions of Beclin-1, autophagy-related 5, and liver kinase B1 (LKB1). These effects of GLA on lipid metabolism disorders of PA-treated hepatocytes were reversed by autophagy inhibitor 3MA and AMPK inhibitor compound C, confirming our conclusions. Overall, GLA can protect AML-12 cells from lipid metabolism disorder caused by PA via balancing autophagy and apoptosis mediated by the LKB1-AMPK-mTOR pathway. Consequently, GLA, as a dietary supplement, can help to prevent and treat NAFLD by regulating lipid metabolism and autophagy.

中文翻译：

γ-亚麻酸通过 LKB1-AMPK-mTOR 通路平衡自噬和凋亡，预防棕榈酸处理的 α 小鼠肝脏 12 细胞的脂质代谢紊乱

脂肪沉积过多是非酒精性脂肪肝（NAFLD）的主要特征，而γ-亚麻酸（GLA）是一种多不饱和脂肪酸，可以减少脂质沉积。本研究调查了 GLA (100 μM) 对经 400 μM 棕榈酸 (PA) 处理的 α 小鼠肝 12 (AML-12) 细胞脂质代谢的影响和调节机制。GLA 降低了脂质含量并增加了脂肪酸 β 氧化，这通过降低甘油三酯和胆固醇含量以及增加 CPT1α 和 PPARα 的 mRNA 和蛋白质表达来表明。GLA 可减轻 PA 引起的氧化应激，上调超氧化物歧化酶和谷胱甘肽过氧化物酶的 mRNA 水平，并降低活性氧含量。GLA 减少了细胞凋亡，如 BAX/BCL2 表达水平和细胞凋亡百分比的降低所示。GLA 激活自噬，自噬体-溶酶体融合、LKB1-AMPK-mTOR 信号传导以及 Beclin-1、自噬相关 5 和肝激酶 B1 (LKB1) 的 mRNA 和蛋白质表达上调。GLA 对 PA 处理的肝细胞脂质代谢紊乱的这些影响被自噬抑制剂 3MA 和 AMPK 抑制剂化合物 C 逆转，证实了我们的结论。总的来说，GLA 可以通过平衡 LKB1-AMPK-mTOR 通路介导的自噬和细胞凋亡来保护 AML-12 细胞免受 PA 引起的脂质代谢紊乱。因此，GLA 作为一种膳食补充剂，可以通过调节脂质代谢和自噬来帮助预防和治疗 NAFLD。GLA 对 PA 处理的肝细胞脂质代谢紊乱的这些影响被自噬抑制剂 3MA 和 AMPK 抑制剂化合物 C 逆转，证实了我们的结论。总的来说，GLA 可以通过平衡 LKB1-AMPK-mTOR 通路介导的自噬和细胞凋亡来保护 AML-12 细胞免受 PA 引起的脂质代谢紊乱。因此，GLA 作为一种膳食补充剂，可以通过调节脂质代谢和自噬来帮助预防和治疗 NAFLD。GLA 对 PA 处理的肝细胞脂质代谢紊乱的这些影响被自噬抑制剂 3MA 和 AMPK 抑制剂化合物 C 逆转，证实了我们的结论。总的来说，GLA 可以通过平衡 LKB1-AMPK-mTOR 通路介导的自噬和细胞凋亡来保护 AML-12 细胞免受 PA 引起的脂质代谢紊乱。因此，GLA 作为一种膳食补充剂，可以通过调节脂质代谢和自噬来帮助预防和治疗 NAFLD。

更新日期：2021-07-28

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