Endocrine Abstracts (2019) 65 OC1.2 | DOI: 10.1530/endoabs.65.OC1.2

Hepatic de novo lipogenesis is suppressed and fat oxidation is increased by omega-3 fatty acids at the expense of glucose metabolism

Charlotte Green, Camilla Pramfalk, Catriona Charlton, Pippa Gunn, Thomas Cornfield, Michael Pavalides, Fredrik Karpe & Leanne Hodson


University of Oxford, Oxford, UK


Background and Aim: Hepatic de novo lipogenesis (DNL) has been implicated in the development of non-alcoholic fatty liver disease (NAFLD). Supplementation with the omega-3 fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decreases intrahepatic triacylglycerol (IHTAG) and plasma TAG concentrations, which is suggested to be mediated through changes in hepatic DNL. We investigated the effects of omega-3 FA supplementation on intrahepatic DNL and FA partitioning using a combination of human in vivo and in vitro cellular studies.

Methods: Thirty-eight healthy males were randomised to take either an omega-3 supplement (4 g/d EPA+DHA as ethyl esters) or placebo (4 g/d olive oil) for 8 weeks; fasting measurements were made at baseline and 8 weeks. The metabolic effects of omega-3 FAs on IHTAG content, hepatic DNL and FA partitioning were investigated using metabolic substrates labelled with stable-isotope labelled tracers. In vitro cellular studies, using a human liver cell-line were undertaken to gain insight into the intrahepatocellular effects of omega-3 FAs.

Results: Body weight remained unchanged in both groups. Fasting plasma TAG concentrations decreased (P<0.01) in the omega-3 FA supplementation group and remained unchanged in the placebo group. Eight weeks of omega-3 FA supplementation decreased (P<0.05) IHTAG, fasting and postprandial hepatic DNL whilst increasing (P<0.05) dietary FA oxidation and plasma glucose concentrations. In vitro cellular studies demonstrated both EPA+DHA were required for the intrahepatocellular effect.

Conclusions: Omega-3 FA supplementation had a potent effect on decreasing hepatic DNL with concomitant increases in 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 non-lipid precursors (e.g. sugars) will have on intra- and extra-hepatic metabolic pathways.