ABSTRACT
AIM: To test the effect of atorvastatin (ATV) and ATV plus ω-3 FAEEs on VLDL-TG metabolism in obese, insulin resistant men. METHODS: We carried out a 6-week randomized, placebo-controlled study to examine the effect of ATV (40 mg/day) and ATV plus ω-3 FAEEs (4 g/day) on VLDL-TG metabolism in 36 insulin resistant obese men. VLDL-TG kinetics were determined using d5 -glycerol, gas chromatography-mass spectrometry and compartmental modelling. RESULTS: Compared with the placebo, ATV significantly decreased VLDL-TG concentration (-40%, p < 0.001) by increasing VLDL-TG fractional catabolic rate (FCR) (+47%, p < 0.01). ATV plus ω-3 FAEEs lowered VLDL-TG concentration to a greater degree compared with placebo (-46%, p < 0.001) or ATV monotherapy (-13%, p = 0.04). This was achieved by a reduction in VLDL-TG production rate (PR) compared with placebo (-32%, p = 0.008) or ATV (-20%, p = 0.03) as well as a reciprocal increase in VLDL-TG FCR (+42%, p < 0.05) compared with placebo. CONCLUSION: In insulin resistant, dyslipidaemic, obese men, ATV improves VLDL-TG metabolism by increasing VLDL-TG FCR. The addition of 4 g/day ω-3 FAEE to statin therapy provides further TG-lowering by lowering VLDL-TG PR.
Subject(s)
Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Heptanoic Acids/administration & dosage , Insulin Resistance , Lipoproteins, VLDL/blood , Obesity/drug therapy , Pyrroles/administration & dosage , Triglycerides/blood , Anticholesteremic Agents/administration & dosage , Apolipoprotein B-100/blood , Atorvastatin , Drug Combinations , Drug Therapy, Combination , Dyslipidemias/drug therapy , Dyslipidemias/metabolism , Humans , Male , Middle Aged , Obesity/metabolism , Treatment OutcomeABSTRACT
BACKGROUND: 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. DESIGN: Thirty-five men with MetS participated in a 16 week randomized controlled dietary intervention study. Apolipoprotein (apo) C-III, apoB-48, remnant-like particle (RLP)-cholesterol, total adiponectin, high-molecular weight (HMW) adiponectin, and retinol-binding protein-4 (RBP-4) concentrations were measured using immunoassays. RESULTS: Compared with weight maintenance (n = 15), weight loss (n = 20) significantly decreased body weight, plasma insulin, triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and lathosterol (P < 0.05). Weight loss also decreased plasma concentrations of apoC-III (-33%), apoB-48 (-37%), very low-density lipoprotein (VLDL)-apoB (-43%), RLP-cholesterol (-48%), and RBP-4 (-20%), and significantly increased plasma total (+20%) and HMW-adiponectin (+19%) concentrations. In the weight loss group, reduction in plasma apoC-III was associated (P < 0.05) with reduction in plasma apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides. Increase in total adiponectin was associated (P < 0.05) with the reduction in plasma VLDL-apoB and triglycerides. The changes in HMW-adiponectin and RBP-4 were not associated with changes in plasma apoB-48, apoC-III, VLDL-apoB, RLP-cholesterol or triglycerides. In multiple regression analysis including changes in visceral fat, insulin and total adiponectin concentrations, the fall in plasma apoC-III concentration was an independent predictor of the reductions in plasma apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides concentrations. CONCLUSIONS: In men with MetS, weight loss decreases the plasma concentrations of apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides. This effect could partly relate to concomitant changes in plasma apoC-III and adiponectin concentrations that accelerate the catabolism of TRLs.
Subject(s)
Lipoproteins/metabolism , Metabolic Syndrome/metabolism , Triglycerides/metabolism , Weight Loss , Adult , Apolipoprotein B-48/analysis , Apolipoprotein C-III/analysis , Apolipoproteins B/analysis , Biomarkers/analysis , Cholesterol/analysis , Cytokines/analysis , Enzyme-Linked Immunosorbent Assay , Humans , Linear Models , Male , Metabolic Syndrome/diet therapy , Middle AgedABSTRACT
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. METHODS: LFAT was quantified by MRI and MRS in 17 free-living, healthy men with a wide range of body mass indexes. Fasting adiponectin was measured by immunoassay and insulin resistance by homeostasis assessment (HOMA) score. Intraperitoneal, retroperitoneal, anterior subcutaneous and posterior subcutaneous abdominal adipose tissue masses (ATMs) were determined by MRI. RESULTS: Measurements of LFAT by MRI and MRS were highly correlated (r = 0.851, p < 0.001). In univariate regression analysis, LFAT by MRI was also significantly correlated with plasma triglycerides (TGs), insulin, HOMA score, carbohydrate intake and the masses of all abdominal adipose tissue compartments (p < 0.05). LFAT was inversely correlated with plasma adiponectin (r = -0.505, p < 0.05). In multivariate linear regression analysis including plasma adiponectin and age, intraperitoneal ATM was an independent predictor of LFAT (beta-coefficient = 0.587, p = 0.024). Moreover, intraperitoneal ATM was also an independent predictor of HOMA score after adjusting for LFAT, plasma adiponectin and age (beta-coefficient = 0.810, p = 0.010). Conversely, LFAT was a significant predictor of plasma TG concentration after adjusting for adiponectin, intraperitoneal ATM, HOMA and age (beta-coefficient = 0.751, p = 0.007). Similar findings applied with LFAT measured by MRS. CONCLUSIONS: These data suggest that MRI is as good as MRS to quantify liver fat content. Our data also suggest that liver fat content could link intraabdominal fat with insulin resistance and dyslipidaemia.
Subject(s)
Adipose Tissue/anatomy & histology , Body Fat Distribution , Insulin Resistance/physiology , Lipids/blood , Liver/anatomy & histology , Adiponectin/blood , Anthropometry/methods , Humans , Lipoproteins/blood , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Male , Middle Aged , Reproducibility of Results , Triglycerides/bloodABSTRACT
OBJECTIVE: We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol in postmenopausal women with type 2 diabetes mellitus. PATIENTS AND MEASUREMENTS: Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2-week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant-like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope-ratio mass spectrometry and multicompartmental modelling. Plasma apo B-48 and RLP-cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism. RESULTS: Pravastatin significantly reduced plasma concentrations of cholesterol (5.9 +/- 0.3 vs. 4.8 +/- 0.2 mmol/l; P < 0.001), low density lipoprotein (LDL)-cholesterol (3.5 +/- 0.2 vs. 2.6 +/- 0.2 mmol/l; P < 0.001), triglyceride (2.1 +/- 0.3 vs. 1.7 +/- 0.2 mmol/l; P = 0.017), non-high density lipoprotein (HDL)-cholesterol (4.4 +/- 0.3 vs. 3.3 +/- 0.2 mmol/l; P < 0.001), lathosterol/total cholesterol ratio (2.6 +/- 0.2 vs. 2.0 +/- 0.3, P = 0.035), apo B-100 (1.1 +/- 0.1 vs. 0.8 +/- 0.1 g/l; P = 0.001), apo B-48 (4.8 +/- 0.9 vs. 3.3 +/- 0.6 mg/l; P = 0.016), and RLP-cholesterol (31.4 +/- 8.2 vs. 18.6 +/- 4.6 mg/dl; P = 0.024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2.8 +/- 0.3 vs. 3.1 +/- 0.3, P = 0.029). Chylomicron remnant-like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements. CONCLUSIONS: In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.
Subject(s)
Anticholesteremic Agents/therapeutic use , Chylomicrons/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Pravastatin/therapeutic use , Aged , Apolipoprotein B-48 , Apolipoproteins B/blood , Breath Tests , Carbon Isotopes/blood , Cholesterol/blood , Cholesterol, LDL/blood , Chylomicron Remnants , Chylomicrons/blood , Cross-Over Studies , Diabetes Mellitus, Type 2/diet therapy , Female , Humans , Mass Spectrometry , Metabolic Clearance Rate/drug effects , Middle Aged , Triglycerides/bloodABSTRACT
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/m(2)). METHODS: Using enzyme immunoassays, plasma adiponectin and resistin were measured. Intraperitoneal, retroperitoneal, subcutaneous abdominal and posterior subcutaneous abdominal adipose tissue masses (IPATM, RPATM, SAATM and PSAATM, respectively) were determined using magnetic resonance imaging. Total adipose tissue mass (TATM) was measured using bioelectrical impedance. Insulin resistance was estimated with the help of homeostasis model assessment (HOMA) score. RESULTS: In univariate regression, plasma adiponectin levels were inversely related to IPATM (r = -0.389, p < 0.05), SAATM (r = -0.500, p < 0.001), PSAATM (r = -0.502, p < 0.001), anterior SAATM (r = -0.422, p < 0.01) and TATM (r = -0.421, p < 0.01). In multiple regression models, adiponectin was chiefly correlated with PSAATM. Plasma adiponectin concentrations were also inversely correlated with HOMA score (r = -0.540, p < 0.001) and triglyceride (r = -0.632, p < 0.001), and positively correlated with high-density lipoprotein cholesterol (r = 0.508, p < 0.001). There were no significant correlations between resistin levels and adipose tissue masses, insulin resistance or dyslipidaemia. CONCLUSIONS: In men, total body fat is significantly correlated with plasma adiponectin, but not with plasma resistin levels. Low plasma adiponectin levels appear to be chiefly determined by the accumulation of posterior subcutaneous abdominal fat mass, as opposed to intra-abdominal fat, and are strongly predictive of insulin resistance and dyslipidaemia.