University of Oxford, Oxford, Oxfordshire, UK.
Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
BMJ Open Diabetes Res Care. 2020 Mar;8(1). doi: 10.1136/bmjdrc-2019-000871.
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.
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.
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.
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.
NCT01936779.
肝从头合成脂肪酸（DNL）增加被认为是导致非酒精性脂肪肝和/或胰岛素抵抗的潜在原因。有研究表明ω-3 脂肪酸（FA）可降低肝 DNL。本研究通过人体体内和体外研究相结合，探讨了 ω-3 FA 补充对肝 DNL 和 FA 氧化的影响。
38 名健康男性被随机分为 ω-3 补充组（每天 4g 二十碳五烯酸（EPA）+二十二碳六烯酸（DHA）乙酯）或安慰剂组（每天 4g 橄榄油），并在基线和 8 周时进行空腹测量。使用稳定同位素示踪剂标记的代谢底物，研究 ω-3 FA 对肝细胞内三酰甘油（IHTAG）含量、肝 DNL 和 FA 氧化的代谢影响。体外研究使用人肝细胞系，以深入了解 ω-3 FA 对肝细胞内的影响。
ω-3 组空腹血浆 TAG 浓度显著降低，而安慰剂组无变化。8 周的 ω-3 补充显著降低 IHTAG、空腹和餐后肝 DNL，同时显著增加膳食 FA 氧化和空腹及餐后血浆葡萄糖浓度。体外研究支持 ω-3 FA（EPA+DHA）通过改变细胞代谢，从 FA 酯化向氧化转移，减少细胞内 TAG 的体内研究结果。
ω-3 补充对降低肝 DNL 和增加 FA 氧化及血浆葡萄糖浓度有显著作用。降低肝 DNL 可能被认为是有利的；然而，需要考虑到非脂类底物（如葡萄糖）的潜在过剩将对肝内和肝外代谢途径产生什么影响。
NCT01936779。
