Overproduction of large VLDL particles is driven by increased liver fat content in man

Adiels, M. et al. (2006) Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia, 49(4), pp. 755-765. (doi:10.1007/s00125-005-0125-z)

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<b>Aims/hypothesis</b>: We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL1 production. <b>Methods</b>: A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL1 and VLDL2 after a bolus of [2H3]leucine and [2H5]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI. <b>Results</b>: Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL1 TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL1 in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL1 TG and ApoB pool sizes, adiponectin was not linked to VLDL1 TG or ApoB production and thus was not a predictor of VLDL1 production. However, adiponectin correlated negatively with the removal rates of VLDL1 TG and ApoB. <b>Conclusions/interpretation</b>: We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL1 particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Caslake, Professor Muriel and Packard, Professor Chris
Authors: Adiels, M., Taskinen, M.R., Packard, C., Caslake, M.J., Soro-Paavonen, A., Westerbacka, J., Vehkavaara, S., Hakkinen, A., Olofsson, S.O., Yki-Jarvinen, H., and Boren, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences
Journal Name:Diabetologia
ISSN (Online):1432-0428
Published Online:04 February 2006

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