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

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 VLDL1-triacylglycerol (TAG) after the high ( P <0.02) and low sugar ( P <0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet ( P <0.01), and a higher VLDL1-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 VLDL1-TAG ( P <0.02) in the controls, but in contrast, a higher production of VLDL2-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. This 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.The work was supported by a UK government grant from the Biological Biotechnology Scientific Research Council (Grant no. BB/G009899/1); University of Surrey PhD scholarship for AM; Medical Research Council (body composition measurements) and infrastructure support from the National Institute of Health Research at the Cambridge Biomedical Research Centre

Exercise therapy in Type 2 diabetes

Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity

Train crashworthiness and its impact on society

In an environment where resources are scarce, decisions to spend more on safety or risk reduction need to be made on a rational basis. The assessment of such a situation must reflect the impact on society as a whole. When death and injury are involved the assessment, hence becomes very complicated. This paper discusses how societal cost models can assist in making these difficult decisions and an example is analysed based on train crashworthiness

Development of a method to measure preβHDL and αHDL apoA-I enrichment for stable isotopic studies of HDL kinetics

Our understanding of HDL metabolism would be enhanced by the measurement of the kinetics of preβHDL, the nascent form of HDL, since elevated levels have been reported in patients with coronary artery disease. Stable isotope methodology is an established technique that has enabled the determination of the kinetics (production and catabolism) of total HDL apoA-I in vivo. The development of separation procedures to obtain a preβHDL fraction, the isotopic enrichment of which could then be measured, would enable further understanding of the pathways in vivo for determining the fate of preβHDL and the formation of αHDL. A method was developed and optimised to separate and measure preβHDL and αHDL apoA-I enrichment. Agarose gel electrophoresis was first used to separate lipoprotein subclasses, and then a 4-10 % discontinuous SDS-PAGE used to isolate apoA-I. Measures of preβHDL enrichment in six healthy subjects were undertaken following an infusion of L-[1-13C-leucine]. After isolation of preβ and αHDL, the isotopic enrichment of apoA-I for each fraction was measured by gas chromatography-mass spectrometry. PreβHDL apoA-I enrichment was measured with a CV of 0.51 % and aHDL apoA-I with a CV of 0.34 %. The fractional catabolic rate (FCR) of preβHDL apoA-I was significantly higher than the FCR of aHDL apoA-I (p < 0.005). This methodology can be used to selectively isolate preβ and aHDL apoA-I for the measurement of apoA-I isotopic enrichment for kinetics studies of HDL subclass metabolism in a research setting. © AOCS 2012

The effect of age and gender on the metabolic disposal of [1-13C] palmitic acid

Our observations that children oxidised nearly twice the amount of [1-13C]palmitic acid than adults in conjunction with greater net fat oxidation in children than adults in both the postabsorptive and postprandial states should be considered before current UK dietary recommendations for fat and saturated fats, developed for adults, are applied to growing children. For dietary recommendations to be developed further more information is required, particularly in groups of infants and the elderly, about the factors that influence the postprandial handling of dietary fat