Previous studies have demonstrated that saturated fatty acids (SFAs) are more lipotoxic than unsaturated fatty acids (UFAs) in inhibiting hepatic autophagy and promoting non-alcoholic steatohepatitis (NASH). However, there have been few studies have investigated the effects of carbon chain length on SFA-induced autophagy impairment and lipotoxicity. To investigate whether SFAs with shorter carbon chain lengths have differential effects on hepatic autophagy and NASH development, we partially replaced lard with coconut oil to elevate the ratio of medium-chain fatty acids (MCFAs) to long-chain fatty acids (LCFAs) in a mouse high-fat diet (HFD) and fed mice for 16 weeks. In addition, we treated HepG2 cells with different combinations of fatty acids to study the mechanisms of MCFAs-mediated hepatic protections. Our results showed that increasing dietary MCFA/LCFA ratio mitigated HFD-induced Type 2 diabetes and NASH in mice. Importantly, we demonstrated that increased MCFA ratio exerted its protective effects by restoring Rubicon-suppressed autophagy. Our study suggests that the relative amount of LCFAs and MCFAs in the diet, in addition to the amount of SFAs, can significantly contribute to autophagy impairment and hepatic lipotoxicity. Collectively, we propose that increasing dietary MCFAs could be an alternative therapeutic and prevention strategy for Type 2 diabetes and NASH.

中文翻译：

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通过调节自噬，提高膳食中链脂肪酸的比例可以减轻高脂饮食引起的非酒精性脂肪性肝炎。

先前的研究表明，在抑制肝脏自噬和促进非酒精性脂肪性肝炎（NASH）方面，饱和脂肪酸（SFA）比不饱和脂肪酸（UFA）具有更高的脂毒性。但是，很少有研究研究碳链长度对SFA诱导的自噬损伤和脂毒性的影响。为了研究具有较短碳链长度的SFA对肝自噬和NASH发育是否有不同的影响，我们用椰子油部分代替了猪油，以提高猪体内中链脂肪酸（MCFA）与长链脂肪酸（LCFA）的比例。小鼠高脂饮食（HFD），并喂食小鼠16周。此外，我们用脂肪酸的不同组合处理了HepG2细胞，以研究MCFA介导的肝保护机制。我们的结果表明，饮食中MCFA / LCFA比例的增加减轻了HFD诱导的2型糖尿病和NASH。重要的是，我们证明了增加的MCFA比例可通过恢复Rubicon抑制的自噬发挥其保护作用。我们的研究表明，饮食中LCFA和MCFA的相对含量，除了SFA的含量外，还可以显着促进自噬功能障碍和肝脂质毒性。总体而言，我们建议增加饮食中的MCFA可能是2型糖尿病和NASH的替代治疗和预防策略。除了SFA的量外，还可显着促进自噬功能障碍和肝脂毒性。总体而言，我们建议增加饮食中的MCFA可能是2型糖尿病和NASH的替代治疗和预防策略。除SFA的量外，还可显着促进自噬功能障碍和肝脂毒性。总体而言，我们建议增加饮食中的MCFA可能是2型糖尿病和NASH的替代治疗和预防策略。