Molecular Metabolism of Lipids Laboratory, BioMed Research Center, Biological Sciences Department, University of Quebec in Montreal (UQAM), Montreal, QC H3C 3P8, Canada.
Molecules. 2018 Sep 11;23(9):2315. doi: 10.3390/molecules23092315.
Metabolic illnesses such as non-alcoholic fatty liver disease (NAFLD) are in constant increase worldwide. Highly consumed long chain fatty acids (LCFA) are among the most obesogenic and steatogenic nutrients. Hepatic steatosis is associated with several complications such as insulin resistance. Growing evidence points to medium chain fatty acids (MCFA), more efficiently oxidized than LCFA, as a promising dietary alternative against NAFLD. However, reports on the hepatic effects of MCFA are sometimes conflicting. In this study we exposed HepG2 cells, a human hepatocellular model, to 0.25 mM of hexanoic (C6), or octanoic (C8), and decanoic (C10) acids separately or in a C8 + C10 equimolar mix reflecting commercially available MCFA-rich oils. We found that C6, a poorly studied MCFA, as well as C8 and C10 did not provoke the deleterious lipid anabolism runaway typically induced by LCFA palmitate. MCFA tended, instead, to promote a balanced metabolic profile and were generally non-cytotoxic. Accordingly, mitochondrial integrity was mostly preserved following MCFA treatment. However, treatments with C8 induced a mitochondrial membrane potential decrease, suggesting prolonged exposure to this lipid could be problematic. Finally, MCFA treatments maintained optimal insulin sensitivity and even fostered basal and insulin-dependent phosphorylation of the Akt-mTOR pathway. Overall, MCFA could constitute an effective nutritional tool to manage liver steatosis and hepatic insulin resistance.
代谢疾病，如非酒精性脂肪肝疾病（NAFLD），在全球范围内持续增加。高消耗的长链脂肪酸（LCFA）是最肥胖和致脂肪变性的营养物质之一。肝脂肪变性与胰岛素抵抗等多种并发症有关。越来越多的证据表明，中链脂肪酸（MCFA）比 LCFA 更有效地氧化，作为治疗 NAFLD 的一种有前途的饮食选择。然而，关于 MCFA 对肝脏影响的报告有时存在冲突。在这项研究中，我们将 HepG2 细胞（一种人肝细胞模型）暴露于 0.25 mM 的己酸（C6）、辛酸（C8）和癸酸（C10）中，或者分别以反映市售 MCFA 丰富油的 C8+C10 等摩尔混合物的形式暴露。我们发现，C6，一种研究甚少的 MCFA，以及 C8 和 C10 并没有引发通常由 LCFA 棕榈酸引起的有害脂质合成失控。MCFA 反而倾向于促进平衡的代谢特征，通常是非细胞毒性的。因此，在 MCFA 处理后，线粒体完整性大多得以保留。然而，C8 的处理会导致线粒体膜电位降低，表明长时间暴露于这种脂质可能会有问题。最后，MCFA 处理保持了最佳的胰岛素敏感性，甚至促进了 Akt-mTOR 通路的基础和胰岛素依赖性磷酸化。总的来说，MCFA 可以作为一种有效的营养工具来管理肝脂肪变性和肝胰岛素抵抗。
