$Aims/hypothesis:$ We aimed to test the hypothesis that the effects of dietary sugar on lipoprotein metabolism are influenced by non-alcoholic fatty liver disease (NAFLD).

$Methods:$ The effect of two 12 week, iso-energetic diets, high and low in non-milk extrinsic sugars (26% and 6% total energy), matched for macronutrient content, was examined in a randomised, cross-over study in men with NAFLD (n=11) and controls (n= 14). Lipoprotein kinetics and the sources of fatty acids for triacylglycerol (TAG) production were measured using stable isotope tracers.

$Results:$ Liver fat was higher after the high versus low-sugar diet in both groups (p<0.02), but men with NAFLD showed a relatively greater response than controls (p<0.05). After the high versus low-sugar diet, VLDL1-TAG production rate was higher in the controls (p <0.002) due to a greater contribution from splanchnic fatty acids (p<0.02) and de novo lipogenesis (p <0.002), whereas in NAFLD, VLDL2-TAG production rate was higher (p <0.05), due to a greater contribution from splanchnic fatty acids (p<0.02). There was no difference in the contribution of systemic NEFA to VLDL1 and VLDL2-TAG production rate between diets in either group. Intermediate density lipoprotein (IDL), LDL2 and LDL3-apolipoprotein B production rates and post-heparin hepatic lipase activity were all higher (p<0.05) on the high-sugar diet in NAFLD.

$Conclusions:$ A high sugar intake promoted a greater accumulation of liver fat in NAFLD than controls and increased VLDL-TAG production in both groups, due mainly to an increased contribution of fatty acids from splanchnic sources, which includes hepatic TAG storage pools. These effects may drive the formation of atherogenic lipoproteins.