Hepatic de novo lipogenesis is suppressed and fat oxidation is increased by omega-3 fatty acids at the expense of glucose metabolism
Hepatic de novo lipogenesis is suppressed and fat oxidation is increased by omega-3 fatty acids at the expense of glucose metabolism
复制标题
DOI：
10.1136/bmjdrc-2019-000871
复制
发表时间：
2020-01-01
影响因子：
4.1
通讯作者：
Hodson, Leanne
中科院分区：
文献类型：
--
作者：
Green, Charlotte J.;Pramfalk, Camilla;Hodson, Leanne
目的 肝脏从头脂肪生成 (DNL) 增加被认为是非酒精性脂肪肝疾病和/或胰岛素抵抗发展的根本原因。建议 omega-3 脂肪酸 (FA) 降低肝脏 DNL。我们结合人体体内和体外研究研究了 omega-3 FA 补充剂对肝脏 DNL 和 FA 氧化的影响。研究设计和方法 38 名健康男性被随机服用 omega-3 补充剂（4 克/天二十碳五烯酸 (EPA)+二十二碳六烯酸 (DHA) 作为乙酯）或安慰剂（4 克/天橄榄油），并在基线和 8 周进行空腹测量。使用稳定同位素示踪剂标记的代谢底物研究了 omega-3 FA 对肝细胞内三酰甘油 (IHTAG) 含量、肝脏 DNL 和 FA 氧化的代谢影响。使用人类肝细胞系进行体外研究，以深入了解 omega-3 FA 的肝细胞内效应。结果 omega-3 组的空腹血浆 TAG 浓度显着降低，而安慰剂组则保持不变。补充 omega-3 八周可显着降低 IHTAG、空腹和餐后肝脏 DNL，同时显着增加膳食 FA 氧化以及空腹和餐后血浆葡萄糖浓度。体外研究支持了 omega-3 FA (EPA+DHA) 通过将细胞代谢从 FA 酯化转向氧化而减少细胞内 TAG 的体内研究结果。结论补充 Omega-3 对减少肝脏 DNL 和增加 FA 氧化和血浆葡萄糖浓度具有有效作用。肝脏 DNL 的减弱可能被认为是有利的；然而，需要考虑潜在过量的非脂质底物（例如葡萄糖）对肝内和肝外代谢途径的影响。
Objective Increased hepatic de novo lipogenesis (DNL) is suggested to be an underlying cause in the development of nonalcoholic fatty liver disease and/or insulin resistance. It is suggested that omega-3 fatty acids (FA) lower hepatic DNL. We investigated the effects of omega-3 FA supplementation on hepatic DNL and FA oxidation using a combination of human in vivo and in vitro studies.Research design and methods Thirty-eight healthy men were randomized to take either an omega-3 supplement (4 g/day eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) as ethyl esters) or placebo (4 g/day olive oil) and fasting measurements were made at baseline and 8 weeks. The metabolic effects of omega-3 FAs on intrahepatocellular triacylglycerol (IHTAG) content, hepatic DNL and FA oxidation were investigated using metabolic substrates labeled with stable-isotope tracers. In vitro studies, using a human liver cell-line was undertaken to gain insight into the intrahepatocellular effects of omega-3 FAs.Results Fasting plasma TAG concentrations significantly decreased in the omega-3 group and remained unchanged in the placebo group. Eight weeks of omega-3 supplementation significantly decreased IHTAG, fasting and postprandial hepatic DNL while significantly increasing dietary FA oxidation and fasting and postprandial plasma glucose concentrations. In vitro studies supported the in vivo findings of omega-3 FAs (EPA+DHA) decreasing intracellular TAG through a shift in cellular metabolism away from FA esterification toward oxidation.Conclusions Omega-3 supplementation had a potent effect on decreasing hepatic DNL and increasing FA oxidation and plasma glucose concentrations. Attenuation of hepatic DNL may be considered advantageous; however, consideration is required as to what the potential excess of nonlipid substrates (eg, glucose) will have on intrahepatic and extrahepatic metabolic pathways.