Abstract
Background: High sugar diet may increase plasma triacylglycerol (TG) levels and cause dyslipidaemia, resulting in a higher cardiometabolic risk. High sugar intake may also promote the accumulation of ectopic fat in the liver. Objectives: To determine the effect of two isocaloric diets, low and high in extrinsic sugars (6% or 26% total energy respectively corresponding to the lower and upper 2.5th percentile of the intake in men aged 40-65 in the UK) but with the same total carbohydrate content, on fasting plasma TG, liver fat, lipoprotein concentration, and very low density lipoprotein (VLDL) TG kinetics and sources of fatty acids for VLDL-TG synthesis (by stable isotope techniques), in men at increased risk of metabolic syndrome. Study design: Participants were randomised in a two-way cross-over design with two 12-week dietary phases, low or high in extrinsic sugar. Dietary exchange of sugar for starch was achieved using a range of supermarket foods low or high in total sugar (≤10% or ≥40% respectively) consumed in the homes of participants. Participants were divided in two groups, low liver fat (n=14) and high liver fat (n=11) (liver fat < or >5% by magnetic resonance spectroscopy), in order to investigate the impact of liver fat on the lipid response to dietary sugar. Results: Liver fat was higher in both groups after the high sugar diet, although the magnitude of this effect was greater in men with high liver fat (median [IQR] as % liver fat volume: 15.3 [11.8-45.7] vs 11.4 [8.2-25.6]; P=0.018) than in men with low liver fat (1.7 [1.0-6.6] vs 1.4 [0.7-1.9]; P=0.025). VLDL1-TG production was significantly higher after the high sugar diet than the low sugar diet only in men with low liver fat (mean ± SEM: 16603±1406 mg/day vs 12358±1154 mg/day, P=0.001), due mainly to higher contribution of fatty acids from splanchnic sources (6923±1102 mg/day vs 4286±604 mg/day, P=0.008) and from hepatic de novo lipogenesis (1269±402 mg/day vs 526±137 mg/day, P=0.032). On the other hand, VLDL2-TG production was significantly higher after the high sugar diet than the low sugar diet in the high liver fat group (4902±693 mg/day vs 3704±429 mg/day, P=0.019), but not in the low liver fat group, and this was mainly due to a higher contribution of splanchnic sources of fatty acids (3054±459 mg/day vs 1981±277 mg/day, P=0.002). No significant differences in VLDL-TG catabolism were observed. Conclusion: This study showed clear differences in the response of lipid metabolism to sugar intake in the two liver fat groups, especially with regard to liver fat accumulation and VLDL-TG metabolism. Unexpectedly, a major role in these changes was played by the splanchnic sources of fatty acids rather than by systemically derived fatty acids or hepatic de novo lipogenesis. A low sugar intake close to the latest guidelines for sugar consumption in the general population (5% total energy intake according to the World Health Organisation and UK’s Scientific Advisory Committee on Nutrition), may be beneficial in both lipoprotein metabolism and liver fat, thus improving the cardiometabolic health in these individuals, particularly in men with high liver fat.