P.H.R. Barrett

Association of adiponectin and resistin with adipose tissue compartments, insulin resistance and dyslipidaemia

Aim:  In this study, we investigated the association of plasma adiponectin and resistin concentrations with adipose tissue compartments in 41 free‐living men with a wide range of body mass index (22–35 kg/m2).

Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity

Background  Dyslipidaemia may account for increased risk of cardiovascular disease in central obesity. Pharmacotherapy is often indicated in these patients, but the optimal approach remains unclear. We investigated the effects of atorvastatin and fish oil on plasma lipid and lipoprotein levels, including remnant‐like particle‐cholesterol and apolipoprotein C‐III, in dyslipidaemic men with visceral obesity.

Effect of a statin on hepatic apolipoprotein B-100 secretion and plasma campesterol levels in the metabolic syndrome

OBJECTIVE: We aimed to study the effect of atorvastatin, a statin, on cholesterol synthesis and absorption and VLDL-apoB metabolism in obese men with the metabolic syndrome.METHODS: A total of 25 dyslipidaemic obese men were randomized to atorvastatin (n=13) (40 mg/day) or matching placebo (n=12) for 6 weeks. Hepatic secretion and fractional catabolic rate (FCR) of VLDL-apoB was measured using an intravenous bolus of d3-leucine before and after treatment. ApoB isotopic enrichment was measured using GCMS and multicompartmental modelling. Plasma lathosterol: cholesterol and campesterol:cholesterol ratios were determined to assess cholesterol synthesis and cholesterol absorption, respectively.RESULTS: Compared with placebo, atorvastatin significantly decreased (P<0.05) total cholesterol, triglyceride, LDL-cholesterol and VLDL-apoB. Plasma lathosterol:cholesterol ratio decreased from 26.4±2.4 to 8.8±0.8, while the campesterol:cholesterol ratio increased from 26.5±4.4 to 38.6±5.8 (P<0.01). Atorvastatin also increased VLDL-apoB FCR from 3.82±0.33 to 6.30±0.75 pools/day (P<0.01), but did not significantly alter VLDL-apoB secretion (12.8±1.7 to 13.8±2.0 mg/kg/day).CONCLUSIONS: In obesity, atorvastatin inhibits cholesterogenesis but increases intestinal cholesterol absorption. The increased cholesterol absorption may counteract the inhibitory effect on hepatic VLDL-apoB secretion, but it does not apparently influence enhanced catabolism of VLDL-apoB.

Measurement of liver fat by magnetic resonance imaging: relationships with body fat distribution, insulin sensitivity and plasma lipids in healthy men

Aim:  We compared the use of magnetic resonance imaging (MRI) as a test for liver fat content (LFAT) with proton magnetic resonance spectroscopy (MRS) and investigated its relationship with body fat distribution, insulin sensitivity, plasma lipids and lipoproteins.

Elevated apolipoprotein B‐48 and remnant‐like particle–cholesterol in heterozygous familial hypercholesterolaemia

Apolipoprotein B‐48 (apoB‐48) is a marker of triglyceride‐rich lipoprotein (TRL) remnants of intestinal origin. Chylomicron remnants are causally related to atherosclerosis. We have shown previously that fasting plasma apoB‐48 may predict postprandial lipaemia. Remnant‐like particle–cholesterol (RLP‐C) may also reflect TRL remnants. We aimed to determine whether subjects with heterozygous familial hypercholesterolaemia (FH) had an accumulation of remnants of intestinal origin, as reflected by fasting plasma apoB‐48 and RLP‐C levels.

Effect of weight loss on markers of triglyceride‐rich lipoprotein metabolism in the metabolic syndrome

Backgroud  Hypertriglyceridaemia, a consistent feature of dyslipidaemia in the metabolic syndrome (MetS), is related to the extent of abdominal fat mass and altered adipocytokine secretion. We determined the effect of weight loss by dietary restriction on markers of triglyceride‐rich lipoprotein (TRL) metabolism and plasma adipocytokines.

Chylomicron remnant metabolism studied with a new breath test in postmenopausal women with and without type 2 diabetes mellitus

objectives The kinetic basis for the effect of type 2 diabetes mellitus (DM) on postprandial lipoproteins has not been fully established. We investigated chylomicron remnant metabolism using a stable isotope breath test and fasting measurements of plasma apolipoprotein (apo) B‐48 and apoC‐III concentrations in postmenopausal women with and without type 2 DM.

Effect of Dietary Fatty Acids on Human Lipoprotein Metabolism: A Comprehensive Update

Dyslipidemia is a major risk factor for cardiovascular disease (CVD). Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high n-3 polyunsaturated fatty-acids (PUFA) consumption diminished hepatic triglyceride-rich lipoprotein (TRL) secretion and enhanced TRL to low-density lipoprotein (LDL) conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased very low-density lipoprotein (VLDL) cholesterol and triglyceride concentrations by up-regulating VLDL lipolysis and uptake. In a study of healthy subjects, the intake of saturated fatty-acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia. Low medium-chain triglyceride may not appreciably alter TRL metabolism. Replacing carbohydrate with monounsaturated fatty-acids increased TRL catabolism. Trans-fatty-acid decreased LDL and enhanced high-density lipoprotein catabolism. Interactions between APOE genotype and n-3 PUFA in regulating lipid responses were also described. The major advances in understanding the effect of dietary fatty-acids on lipoprotein metabolism has centered on n-3 PUFA. This knowledge emphasizes the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potentially CVD risk. Additional studies are required to better characterize the cardiometabolic effects of other dietary fatty-acids.

Kinetic studies of lipoprotein metabolism in the metabolic syndrome including effects of nutritional interventions

Nutritional interventions may favourably regulate dyslipoproteinemia and, hence, decrease cardiovascular disease risk. Lipoprotein kinetic studies afford a powerful approach to understanding and defining the mechanisms by which such interventions modulate lipoprotein metabolism. Stable isotope tracers and compartment models are now commonly employed for such studies. We review the recent application of tracer methodologies to the study of dyslipoproteinemia in the metabolic syndrome. We also focus on the effects of nutritional intervention studies that have addressed the effects of weight loss, n-3 fatty acids, plant sterols and alcohol on very low density lipoprotein, LDL and HDL metabolism. The potential for statin treatment as an adjunct to dietary modification is also discussed. New tracer methodologies are discussed, specifically those referring to reverse cholesterol transport. The nutritional interventions discussed in this review are readily transferable into clinical preventive practice. The potential benefits to be gained by weight loss and fish oil supplementation in the metabolic syndrome extend beyond their specific and positive effects on lipoprotein metabolism. Furthermore, recent developments in tracer methodologies afford new tools for probing the in-vivo pathways of lipoprotein metabolism in future studies.

ATP-Binding Cassette Transporter G8 Gene As a Determinant of Apolipoprotein B-100 Kinetics in Overweight Men

Objective—We examined the influence of genetic variation of the ATP-binding cassette (ABC) transporter G8 on apolipoprotein B (apoB) kinetics in overweight/obese men. Methods and Results—Very low–density lipoprotein (VLDL) and low-density lipoprotein (LDL) apoB kinetics were determined in 47 men (body mass index 32±3 kg/m2) using stable isotope and multicompartmental modeling to estimate production rate (PR), fractional catabolic rate (FCR), and VLDL to LDL–apoB conversion. Relative to the wild-type (400TT), subjects carrying the ABCG8 400K allele had significantly decreased plasma concentrations of triglycerides, sitosterol, and campesterol, lower PR of VLDL–apoB, and higher VLDL to LDL–apoB conversion (P<0.05). The PR and FCR of LDL–apoB were also significantly higher with 400K allele (P<0.05). No association was found with ABCG8 D19H. Compared with APOE2 or APOE3, APOE4 carriers had significantly higher plasma LDL-cholesterol concentrations and lower LDL–apoB FCR. During multiple regression analysis including age, homeostasis model assessment score, plasma concentrations of sitosterol, and lathosterol, ABCG8 and apoE genotypes were independent determinants of VLDL–apoB PR and LDL–apoB FCR, respectively (P<0.05). Conclusions—Variation in the ABC transporter G8 appears to independently influence the metabolism of apoB-containing lipoproteins in overweight/obese subjects. This may have therapeutic implications for the management of dyslipidemia in these subjects.