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

Structure of chordae tendineae in the left ventricle of the human heart

The bicuspid (mitral) valve complex of the human heart consists of functional units which include the valve leaflets, chordae tendineae and the papillary muscles. The mechanical properties of these functional units depend to a large extent on the link between the muscle and the valve. This link is usually arranged in a branching network of avascular tendinous chordae composed of collagen and elastic fibres, which transmit contractions of the papillary muscle to the valve leaflets. In order to perform their function efficiently, the chordae have to possess a high degree of elasticity, as well as considerable strength and endurance. Human chordae tendineae originating from the left ventricles were obtained from 7 embalmed cadavers and 6 postmortem subjects of various ages. Samples washed in saline were fixed or postfixed in 9% formol saline. Observations were made by illuminating the chordae along their axes. The reflected images originating from the superficial collagenous layers of the relaxed chordae showed a striped pattern 11 μm in width. Scanning electron and light microscopy of the chordae confirmed an undulating pattern of collagen fibrils arranged in bundles of planar waves in register and around the entire circumference of the chorda. The dimensions of the waves correlated with those of the striped reflected pattern. The observed undulating arrangement of the collagen fibrils appears to produce an inherent built-in elasticity which is likely to be of considerable advantage for a tissue which is under continuous repetitive stress. The chordae were covered by endocardium composed of a superficial layer of smooth squamous endothelial cells and an underlying dense layer of elastic fibres. It is suggested that the relaxed striped chordae, consisting of undulating collagen fibrils, straighten when the chordae become stretched by papillary muscle contraction, thereby mitigating the peak stress developed during muscle contraction. On relaxation the elastic tissue tends to return the collagen to its wavy configuration. It is also suggested that the regular wavy pattern of collagen seen in young individuals gradually changes with age by elongation of the wave pattern which eventually becomes randomised. In addition, with increasing age, substantial cushions of connective tissue appear below endocardium while the dense collagenous core has a reduced cross-sectional area which may lead to stretching and eventual rupture of the chordae