Clinical Science (2003) 104, 383-388 - D.C. Chan and others - Cholesterol absorption and triacylglycerol-rich lipoprotein remnant metabolism

Medline/PubMed Citation | Related Articles in PubMed | Download to Citation Manager

Clinical Science (2003) 104, (383–388) (Printed in Great Britain)

PDF

Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome

Dick C. CHAN*, Gerald F. WATTS*, P. Hugh R. BARRETT*, Frans H. O'NEILL†, Trevor G. REDGRAVE‡ and Gilbert R. THOMPSON†

*University Department of Medicine, University of Western Australia, Western Australian Institute for Medical Research, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia, †MRC Clinical Science Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, U.K., and ‡University Department of Physiology, University of Western Australia, Stirling Hwy, Nedlands, Perth, WA 6907, Australia

Key words: breath test, campesterol, cholesterol absorption, chylomicron remnant metabolism, dyslipidaemia.

Abbreviations: apo, apolipoprotein; FCR, fractional catabolic rate; HDL, high-density lipoprotein; HOMA, homoeostasis model assessment; LDL, low-density lipoprotein; MS, metabolic syndrome; NEFA, non-esterified fatty acid; RLP-C, remnant-like particle-cholesterol; TRL, triacylglycerol-rich lipoprotein; VLDL, very-low-density lipoprotein.

The dysmetabolic syndrome of insulin resistance and visceral obesity is characterized by elevated plasma concentration of triacylglycerol-rich lipoprotein (TRL) remnants that may be related to increased cardiovascular risk. Perturbed hepato-intestinal cholesterol metabolism may play a contributory role in this abnormality. We therefore investigated the association between plasma markers of cholesterol absorption and synthesis with TRL remnant metabolism in 35 men with the metabolic syndrome (MS). Plasma campesterol:cholesterol and lathosterol:cholesterol ratios were measured as estimates of cholesterol absorption and synthesis respectively. Remnant metabolism was assessed by measuring remnant-like particle-cholesterol (RLP-C), apolipoprotein (apo)B-48 and the fractional catabolic rate (FCR) of a labelled remnant-like emulsion. Compared with controls, subjects with the MS had significantly lower plasma campesterol:cholesterol ratio, but higher lathosterol:cholesterol ratio (P<0.05). Plasma RLP-C and apoB-48 concentrations were also higher (P<0.01) and the remnant-like emulsion FCR was lower (P<0.05). The plasma campesterol:cholesterol ratio was inversely correlated (P<0.05) with plasma triacylglycerols (r =-0.346), RLP-C (r =-0.443), apoB-48 (r =-0.427) and plasma lathosterol:cholesterol ratio (r =-0.366); the campesterol:cholesterol ratio was also positively correlated with the remnant-like emulsion FCR (r = 0.398, P<0.05). In multiple regression analysis, the significant correlations between plasma campesterol:cholesterol ratio and plasma triacylglycerols, RLP-C, apoB-48 and FCR of the remnant-like emulsion were independent of age, dietary energy and plasma lathosterol. Our findings suggest that in subjects with the MS alterations in cholesterol absorption and synthesis may be closely linked with the kinetic defects in TRL metabolism.