Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets

Abstract

Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n = 11) and low liver fat 'controls' (n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling. There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL 1 -triacylglycerol (TAG) after the high (P<0.02) and low sugar (P<0.0002) diets, a lower VLDL 1 -TAG fractional catabolic rate after the high sugar diet (P<0.01), and a higher VLDL 1 -TAG production rate after the low sugar diet (P<0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL 1 -TAG (P<0.02) in the controls, but in contrast, a higher production of VLDL 2 -TAG (P<0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.

Impact of the occupational environment of a submerged submarine on cardiometabolic health of Royal Navy submariners

“…While ‘high-quality diets’ consisting of high intakes of fruits and vegetables, whole grains and certain dairy products have been associated with protective effects against MetS,38 such diets are difficult to achieve in a submarine environment without regular replenishment of foods during the patrol. At high levels of intake, similar to that reported in RN submariners (~20% of intake), free sugars have been shown to produce adverse effects on cardiometabolic risk factors in the short term,39 40 although this effect is more often associated with elevated serum TG and not cholesterol. Submerged submariners showed trends towards lower intakes of energy and macronutrients and a significant decrease in sugar at the later stage of patrol, such that negative energy balance might have been likely if activity patterns remained similar.…”

The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state

“…Dietary influences on VLDL secretion have been reported in a limited number of studies. A study has compared the influence of isocaloric diets high (26% total energy) and low (6% total energy) in free sugars, consumed for 12 weeks, on VLDL-TAG kinetics in individuals with and without NAFLD 154 . While the VLDL1-TAG production rate increased in individuals with and without NAFLD after the high sugar diet, the VLDL2 production rate only increased after the high sugar diet in the individuals with NAFLD 154 .…”

“…A study has compared the influence of isocaloric diets high (26% total energy) and low (6% total energy) in free sugars, consumed for 12 weeks, on VLDL-TAG kinetics in individuals with and without NAFLD 154 . While the VLDL1-TAG production rate increased in individuals with and without NAFLD after the high sugar diet, the VLDL2 production rate only increased after the high sugar diet in the individuals with NAFLD 154 . In participants who were healthy or had hypertriglyceridaemia, a 5-week high carbohydrate (68% total energy) diet resulted in elevated VLDL-TAG concentrations and a reduction in VLDL-TAG uptake compared with a 1-week control diet (carbohydrate 50% total energy), but responses did not differ between the groups 155 .…”

Two weeks of high‐fat feeding disturb lipid and cholesterol molecular markers

“…Although identification of the exact mechanism is beyond the scope of the present study, there are connecting pathways between triglycerides and cholesterol in the liver that may be pointed at. VLDL production is increased in men with NAFLD . To our knowledge, it is unknown if an increase in VLDL production stimulates incorporation of cholesterol into this particle.…”

“…VLDL production is increased in men with NAFLD. 24 To our knowledge, it is unknown if an increase in VLDL production stimulates incorporation of cholesterol into this particle. This in turn might transiently reduce liver cholesterol levels and stimulate a change in LDL-R.…”