Introducing a new component of the metabolic syndrome: low cholesterol absorption.
ABSTRACT Weight reduction is the recommended treatment of obese type 2 diabetes, but the effects of weight reduction on cholesterol metabolism are poorly understood.
We investigated glucose, cholesterol, and lipoprotein metabolism at baseline and 2 y after weight reduction in obese patients with type 2 diabetes consuming an isoenergetic diet.
Sixteen subjects were randomly chosen to consume a very-low-energy or low-energy diet for 3 mo, after which they consumed a weight-maintenance diet for up to 2 y. Cholesterol absorption and metabolism, LDL and HDL kinetics, and variables of glucose metabolism were studied at baseline and 2 y.
Baseline serum sex hormone binding globulin (SHBG) was significantly related to cholesterol absorption efficiency, and serum glucose and insulin concentrations were associated with cholesterol synthesis. After 2 y, body weight was reduced by 6 +/- 1 kg (P < 0.01), body mass index by 6% (P < 0.05), and blood glucose by 14% (P < 0.01); the ratio of serum SHBG to insulin increased by 66% (P < 0.05). Serum and VLDL, LDL, and HDL triacylglycerol were significantly reduced by 13-24%. Despite unchanged serum concentrations of cholesterol, cholesterol absorption efficiency and the ratio of serum plant sterols to cholesterol-indicators of cholesterol absorption-increased by 28% (P < 0.01) and 20-31% (P < 0. 05 for both), respectively; the fractional removal of LDL apolipoprotein B decreased. Fecal excretion of cholesterol as neutral sterols decreased significantly by 11%. Changes in body weight were significantly negatively correlated with changes in ratios of cholesterol to serum plant sterols and cholestanol.
Baseline cholesterol absorption and synthesis were related to respective serum SHBG, glucose, and insulin values. Weight reduction increased cholesterol absorption and improved variables of glucose metabolism. These results suggest that low cholesterol absorption and high synthesis may be part of the insulin resistance syndrome.
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ABSTRACT: We examined serum cholesterol synthesis and absorption markers and their association with neonatal birth weight in obese pregnancies affected by gestational diabetes mellitus (GDM). Pregnant women at risk for GDM (BMI>30 kg/m2) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were collected at six time-points, one in each trimester of pregnancy and at 6 weeks, and 6 and 12 months postpartum. Analysis of cholesterol precursors, cholestanol and plant sterols by GLC revealed that in the first trimester subjects with GDM (n=22) had higher serum Δ8-cholestenol concentration and lathosterol/sitosterol ratio (P<0.05) than the controls (n=30). The ratio of squalene to cholesterol (100 x µmol/mmol of cholesterol) was higher in subjects with GDM in the second (11.5± 0.5 vs. 9.1±0.5, p<0.01) and third (12.1±0.8 vs. 10.0±0.7, p<0.05) trimester. In GDM, the second trimester maternal serum squalene concentration correlated with neonatal birth weight (r = 0.70, p<0.001). In conclusion, in obesity, GDM associated with elevated serum markers of cholesterol synthesis. Correlation of maternal serum squalene with neonatal birth weight suggests potential contribution of maternal cholesterol synthesis to newborn weight in GDM.The Journal of Lipid Research 10/2014; DOI:10.1194/jlr.P049510 · 4.73 Impact Factor
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ABSTRACT: Nut consumption has been studied for its cardio-protective effects. However, the findings of clinical intervention studies are inconsistent, and no intervention studies have been conducted in the Korean population. We hypothesized that nut supplementation may have favorable influence on metabolic markers. Therefore, this study aimed to investigate the effects of nut consumption on metabolic parameters and biomarkers related to inflammation, oxidative stress, and endothelial function in Korean adults with metabolic syndrome. To this end, we designed a randomized, parallel, controlled dietary intervention study (ClinicalTrials.gov NCT02023749). Subjects with metabolic syndrome and a body mass index of ≥23 kg/m2 were randomized to a Control group and the Nut group, which received supplementation with 30 g/day of mixed nuts (walnuts, peanuts, and pine nuts) for 6 weeks. Sixty volunteers were included in the final analysis. Metabolic markers were evaluated at baseline and at the end of the study. Total cholesterol and non-high-density lipoprotein cholesterol levels significantly improved in the Nut group compared to those in the Control group (P = .023 and P = .016, respectively) in women. Biomarkers related to inflammation, oxidative stress, and endothelial function did not significantly change from baseline in either group. Thus, supplementing a usual diet with mixed nuts for 6-weeks had favorable effects on several lipid parameters in Korean women with metabolic syndrome. These findings present a possible mechanism for the cardioprotective effects of nut consumption.Nutrition Research 08/2014; 34(9). DOI:10.1016/j.nutres.2014.08.011 · 2.59 Impact Factor
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ABSTRACT: Lipidomics reveals a remarkable diversity of lipids in human plasma. In this study, we have performed an in-depth lipidomic analysis of human plasma from healthy individuals and subjects with metabolic syndrome (MetS) in order to determine the lipidomic profile that allows prognosis of a pathological subpopulation with altered high-density lipoprotein (HDL) metabolism. The MetS population was categorized as having pathological or nonpathological HDL. Anthropometric parameters, cardiovascular risk markers, and lipoprotein subclasses of HDL and low-density lipoproteins were also evaluated. Lipidomic analysis revealed 357 differential molecules that were clustered (k means) in the two groups. The molecules identified in the whole lipidome showed that MetS subjects presented lower levels of glycerolipids and higher levels of glycerophospholipids with respect to control subjects. In contrast, when only statistically differential lipids were taken into account, differences were found between the two groups in almost cases. Furthermore, levels of saturated fatty acids were higher in patients with pathological HDL levels than in controls, whereas levels of unsaturated fatty acids were lower. These results highlight the potential of lipidomics as a clinical tool for risk assessment and monitoring of disease.-Jové, M., Naudí, A., Portero-Otin, M., Cabré, R., Rovira-Llopis, S., Bañuls, C., Rocha, M., Hernández-Mijares, A., Victor, V. M., Pamplona, R. Plasma lipidomics discloses metabolic syndrome with a specific HDL phenotype.The FASEB Journal 08/2014; DOI:10.1096/fj.14-253187 · 5.48 Impact Factor