Theodore W.K. Ng

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).

Effect of Weight Loss on LDL and HDL Kinetics in the Metabolic Syndrome Associations with changes in plasma retinol-binding protein-4 and adiponectin levels

OBJECTIVE—The purpose of this study was to examine the effect of weight loss on LDL and HDL kinetics and plasma retinol-binding protein-4 (RBP-4) and adiponectin levels in men with the metabolic syndrome. RESEARCH DESIGN AND METHODS—LDL apolipoprotein (apo)B-100 and HDL apoA-I kinetics were studied in 35 obese men with the metabolic syndrome at the start and end of a 16-week intervention trial of a hypocaloric, low-fat diet (n = 20) versus a weight maintenance diet (n = 15) using a stable isotope technique and multicompartmental modeling. RESULTS—Consumption of the low-fat diet produced significant reductions (P < 0.01) in BMI, abdominal fat compartments, and homeostasis model assessment score compared with weight maintenance. These were associated with a significant increase in adiponectin and a fall in plasma RBP-4, triglycerides, LDL cholesterol, and LDL apoB-100 concentration (P < 0.05). Weight loss significantly increased the catabolism of LDL apoB-100 (+27%, P < 0.05) but did not affect production; it also decreased both the catabolic (−13%) and production (−13%) rates of HDL apoA-I (P < 0.05), thereby not altering plasma HDL apoA-I or HDL cholesterol concentrations. VLDL apoB-100 production fell significantly with weight loss (P < 0.05). The increase in LDL catabolism was inversely correlated with the fall in RBP-4 (r = −0.54, P < 0.05) and the decrease in HDL catabolism with the rise in adiponectin (r = −0.56, P < 0.01). CONCLUSIONS—In obese men with metabolic syndrome, weight loss with a low-fat diet decreases the plasma LDL apoB-100 concentration by increasing the catabolism of LDL apoB-100; weight loss also delays the catabolism of HDL apoA-I with a concomitant reduction in the secretion of HDL apoA-I. These effects of weight loss could partly involve changes in RBP-4 and adiponectin levels.

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.

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.

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.

Dietary fatty acids and lipoprotein metabolism: new insights and updates.

Purpose of review Dyslipidemia is a powerful 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 lipoprotein metabolism in humans. Recent findings High dietary fish-derived n-3 polyunsaturated fatty acid (PUFA) consumption diminished hepatic triglyceride-rich lipoprotein (TRL) secretion and enhanced TRL to LDL conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased liver fat, and plasma proprotein convertase subtilisin/kexin type 9, triglycerides, total-cholesterol and LDL-cholesterol concentrations. Intake of saturated fatty acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia, which might be due to decreased triglyceride absorption. Replacing carbohydrate with monounsaturated fatty acids increased TRL catabolism. Ruminant trans-fatty acid decreased HDL cholesterol, but the mechanisms are unknown. A new role for APOE genotype in regulating lipid responses was also described. Summary The major advances in understanding the effect of dietary fatty acids on lipoprotein metabolism have focused on n-3 PUFA. This knowledge provides insights into the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potential CVD risk. Further studies are required to better understand the cardiometabolic effects of other dietary fatty acids.

Metabolomics and ischaemic heart disease

Ischaemic heart disease accounts for nearly half of the global cardiovascular disease burden. Aetiologies relating to heart disease are complex, but dyslipidaemia, oxidative stress and inflammation are cardinal features. Despite preventative measures and advancements in treatment regimens with lipid-lowering agents, the high prevalence of heart disease and the residual risk of recurrent events continue to be a significant burden to the health sector and to the affected individuals and their families. The development of improved risk models for the early detection and prevention of cardiovascular events in addition to new therapeutic strategies to address this residual risk are required if we are to continue to make inroads into this most prevalent of diseases. Metabolomics and lipidomics are modern disciplines that characterize the metabolite and lipid complement respectively, of a given system. Their application to ischaemic heart disease has demonstrated utilities in population profiling, identification of multivariate biomarkers and in monitoring of therapeutic response, as well as in basic mechanistic studies. Although advances in magnetic resonance and mass spectrometry technologies have given rise to the fields of metabolomics and lipidomics, the plethora of data generated presents challenges requiring specific statistical and bioinformatics applications, together with appropriate study designs. Nonetheless, the predictive and re-classification capacity of individuals with various degrees of risk by the plasma lipidome has recently been demonstrated. In the present review, we summarize evidence derived exclusively by metabolomic and lipidomic studies in the context of ischaemic heart disease. We consider the potential role of plasma lipid profiling in assessing heart disease risk and therapeutic responses, and explore the potential mechanisms. Finally, we highlight where metabolomic studies together with complementary -omic disciplines may make further inroads into the understanding, detection and treatment of ischaemic heart disease.

Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease

Moderate chronic kidney disease (CKD) (defined by an estimated glomerular filtration rate of 30–60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age- and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, 2H3]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III (P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was significantly and negatively correlated with apoC-III FCR (r = −0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR (P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR (P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modification of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate CKD.

Apolipoprotein A-II: evaluating its significance in dyslipidaemia, insulin resistance, and atherosclerosis.

Abstract Reduced HDL cholesterol, commonly found in subjects with obesity and type 2 diabetes, is associated with increased risk of cardiovascular disease (CVD). ApoA-II, a constituent apolipoprotein of certain HDL particles, plays an important role in the regulation of cholesterol efflux, HDL remodelling, and cholesteryl ester uptake via its interactions with lipid transfer proteins, lipases, and cellular HDL receptors. Recent studies have linked apoA-II directly with triglyceride and glucose metabolism. Most of the data are, however, derived from cellular systems and transgenic animal models. Direct evidence from human studies is scarce. Clinical studies demonstrate that apoA-II is a strong predictor of risk for CVD. There is no evidence, however, that selective therapeutic modification of apoA-II impacts on atherosclerosis and clinical outcomes. More research is required to investigate further the significance of apoA-II in clinical medicine.

Plasma markers of cholesterol homeostasis in metabolic syndrome subjects with or without type-2 diabetes

AIMS We investigated the associations between indices of cholesterol metabolism and features of the metabolic syndrome (MS) in the presence and absence of type-2 diabetes (T2DM). METHODS Men with the MS (N=140) and 10 age- and sex-matched controls were recruited. Plasma lathosterol and campesterol were measured by gas chromatography-mass spectrometry, and their ratios to total cholesterol were used to estimate cholesterol metabolism. RESULTS Compared with healthy controls, MS subjects had significantly higher lathosterol:cholesterol and lower campesterol:cholesterol ratios (p<0.05). In the MS subjects without T2DM (N=82), campesterol:cholesterol ratio was positively associated with age and negatively associated with plasma triglyceride and insulin concentrations, while in MS subjects with T2DM (N=58), the ratio was positively associated with age and adiponectin concentration, and negatively associated with BMI and insulin. Age and fasting insulin were independent predictors of campesterol:cholesterol ratio in MS subjects with T2DM. There was a significant negative association between plasma lathosterol:cholesterol with campesterol:cholesterol ratio (r=-0.436, p=0.014) in MS subjects without T2DM but not in MS subjects with T2DM. CONCLUSIONS Cholesterol absorption efficiency was lower and cholesterol synthesis higher in MS subjects with or without T2DM compared with healthy individuals. Moreover, the reciprocal relationship between cholesterol synthesis and cholesterol absorption is lost in the presence of diabetes.