Yanwen Wang

Conjugated linoleic acid and obesity control: efficacy and mechanisms

Obesity is associated with high blood cholesterol and high risk for developing diabetes and cardiovascular disease. Therefore, management of body weight and obesity are increasingly considered as an important approach to maintaining healthy cholesterol profiles and reducing cardiovascular risk. The present review addresses the effects of conjugated linoleic acid (CLA) on fat deposition, body weight and composition, safety, as well as mechanisms involved in animals and humans. Animal studies have shown promising effects of CLA on body weight and fat deposition. The majority of the animal studies have been conducted using CLA mixtures that contained approximately equal amounts of trans-10, cis-12 (t10c12) and cis-9, trans-11 (c9t11) isomers. Results of a few studies in mice fed CLA mixtures with different ratios of c9t11 and t10c12 isomers have indicated that the t10c12 isomer CLA may be the active form of CLA affecting weight gain and fat deposition. Inductions of leptin reduction and insulin resistance are the adverse effects of CLA observed in only mice. In pigs, the effects of CLA on weight gain and fat deposition are inconsistent, and no adverse effects of CLA have been reported. A number of human studies suggest that CLA supplementation has no effect on body weight and insulin sensitivity. Although it is suggested that the t10c12 CLA is the antiadipogenic isomer of CLA in humans, the effects of CLA on fat deposition are marginal and more equivocal as compared to results observed in animal studies. Mechanisms through which CLA reduces body weight and fat deposition remain to be fully understood. Proposed antiobesity mechanisms of CLA include decreased energy/food intake and increased energy expenditure, decreased preadipocyte differentiation and proliferation, decreased lipogenesis, and increased lipolysis and fat oxidation. In summary, CLA reduces weight gain and fat deposition in rodents, while produces less significant and inconsistent effects on body weight and composition in pigs and humans. New studies are required to examine isomer-specific effects and mechanisms of CLA in animals and humans using purified individual CLA isomers.

Micellar solubilisation of cholesterol is essential for absorption in humans

Background and aims: Intralumenal bile acid (BA) concentrations have a profound effect on cholesterol absorption. We performed studies to assess the effects of markedly reduced lumenal BA on cholesterol absorption in children with inborn errors in BA synthesis and the role of micellar solubilisation of cholesterol on its absorption in an animal model using human intestinal contents. Methods: We studied five subjects: two with 3β hydroxy-C27 steroid dehydrogenase isomerase deficiency (3-HSD), two with Δ4-3-oxosteroid 5β reductase deficiency (5β reductase), and one with 2-methylacyl CoA racemase deficiency (racemase). Subjects were studied on supplemental BA therapy and three weeks after withdrawal of supplements. During each treatment period a liquid meal was consumed. Duodenal samples were collected and analysed, and cholesterol absorption and cholesterol fractional synthetic rates were measured. Human intralumenal contents were infused in a bile diverted rat lymph fistula model to assess micellar versus vesicular absorption of cholesterol. Results: Without BA supplementation, intralumenal BA concentrations were below the critical micellar concentration (CMC) whereas intralumenal BAs increased to above the CMC in all subjects on BA supplementation. Lumenal cholesterol was carried primarily as vesicles in untreated subjects whereas it was carried as both micelles and vesicles in treated subjects. Cholesterol absorption increased ≈55% in treated compared with untreated subjects (p = 0.041), with a simultaneous 70% decrease in synthesis rates (p = 0.029). In the rat lymph fistula model, minimal vesicular cholesterol was absorbed whereas vesicular and micellar fatty acid and phospholipid were comparably absorbed. Conclusions: Increasing micellar cholesterol solubilisation by supplemental BA in subjects with inborn errors of BA synthesis leads to an improvement in cholesterol absorption and reduction in cholesterol synthesis due to improved micellar solubilisation of cholesterol.

Effects of policosanols and phytosterols on lipid levels and cholesterol biosynthesis in hamsters

The current study was carried out to examine the effects of policosanols and phytosterols, alone and in combination, on lipid profiles, cholesterol biosynthesis, and tissue histopathological changes in hamsters. Fifty male Golden Syrian hamsters, weighing 100 to 120 g, were fed a regular rodent chow for 2 wk before being randomly assigned into 5 groups of 10 animals each fed semisynthetic diets for 4 wk. Group 1 was given a control diet that contained 0.25% cholesterol and 5% fat with a PUFA to saturated FA ratio of 0.4. Groups 2 to 5 were fed the control diet and given Octa-6 [a policosanol mixture from sugar cane was, 25 mg/kg body weight (BW)], Ricewax (a policosanol mixture from rice wax with 50% being converted to the corresponding acids, 50 mg/kg BW), phytosterols (CholestatinTM; 1,000 mg/kg BW), and Ricewax (50 mg/kg BW) plus phytosterols (1,000 mg/kg BW), respectively. The results showed that there was no difference between Octa-6 and Ricewax treatments in any of the lipid parameters measured, and both had similar levels of triglyceride (TG), total cholesterol (T-C), and HDL cholesterol (HDL-C) as the control. Octa-6 but not Ricewax increased (P=0.03) non-HDL-C as compared with the control. Phytosterols reduced T-C (P<0.0003) and HDL-C (P<0.004) without a significant effect on TG and non-HDL-C as compared to the control. Ricewax plus phytosterols had effects similar to those with phytosterols alone. Free cholesterol synthetic rates were not different among the treatments. Policosanols or phytosterols did not show any toxic effects in liver, heart, brain, or kidney. Results suggest that, although phytosterols reduce T-C and HDL-C levels, policosanols have no significant favorable effect in changing lipid levels in hamsters.

Effects of Early Cholesterol Intake on Cholesterol Biosynthesis and Plasma Lipids Among Infants Until 18 Months of Age

Background. The endogenous cholesterol fractional synthesis rate (FSR) is related inversely to infant dietary cholesterol at 4 months of age; however, it remains to be established whether this effect is permanent, possibly contributing to later hypercholesterolemia. Objective. To determine whether levels of dietary cholesterol in infancy induced changes in FSR and plasma lipid levels that persisted at 18 months. Methods. A prospective clinical trial was conducted with 47 infants, from their first week of life until 18 months of age, who received human milk (HM) until weaned (n = 15) or were randomized to receive modified cows milk formula (MCF) with added cholesterol (n = 15) or cows milk formula (CF) (n = 17) for 12 months. Cholesterol contents of HM, MCF, and CF were 120, 80, and 40 mg/L, respectively. FSR and plasma lipid levels were measured at 4 and 18 months. Results. At 4 months, total cholesterol and low-density lipoprotein cholesterol levels were higher for infants fed HM and MCF, compared with CF. High-density lipoprotein cholesterol levels were higher in the MCF group than in the HM and CF groups. FSR in the HM group (0.034 ± 0.005 pools per day) was lower than that in the CF group (0.052 ± 0.005 pools per day). There was no difference between the HM and MCF (0.047 ± 0.005 pools per day) groups or between the MCF and CF groups. At 18 months, there were no differences in FSRs or plasma lipid profiles between the groups. Conclusion. Although cholesterol intake before weaning affects FSRs and plasma lipid profiles at 4 months, these differences do not persist after weaning to an unrestricted diet at 18 months. This provides additional evidence that there is no imprinting of FSR in infancy with differing dietary levels of cholesterol.

Validation of a single-isotope-labeled cholesterol tracer approach for measuring human cholesterol absorption

Cholesterol absorption is frequently determined using the plasma dual stable-isotope ratio method (PDSIRM). However, this method involves intravenous injection of stableisotope-labeled cholesterol with simultaneous oral administration of differently labeled cholesterol, which results in high study costs and involves additional ethical considerations. The objective of the present study was to validate a simpler singleisotope method for determining cholesterol absorption against PDSIRM by using data from two previous studies. Enrichments of carbon-13 (13C) and deuterium in red blood cells were analyzed by using differential isotope ratio MS. The area under the curve of 13C-enrichment in the plasma free-cholesterol pool was found to be significantly correlated with cholesterol absorption measured by using PDSIRM for study 1 (r=0.85, P<0.0001) and study 2 (r=0.81, P<0.0001). Average 13C-enrichment correlated with the area under the curve of 13C-enrichment in the plasma free cholesterol for both study 1 (r=0.98, P<0.0001) and study 2 (r=1.00, P<0.0001). Study 1 examined the efficacy and mechanisms of unesterified plant sterols and stanols on lipid profiles in hypercholesterolemic men and women, while study 2 investigated the effects of phytosterol vs. phytostanol esters on plasma lipid levels and cholesterol kinetics in hyperlipidemic men. Experimental approaches to determine cholesterol absorption were identical between the two studies. Consequently, in both studies, correlations (r=0.88, P<0.0001 for study 1, and r=0.82, P<0.0001 for study 2) were found between the average 13C-enrichment of plasma free cholesterol and cholesterol absorption measured by PDSIRM. These results suggest that a single-isotope-labeled cholesterol tracer approach can be used as a reliable noninvasive method to replace PDSIRM for examining changes in cholesterol absorption.

Effects of a water-soluble phytostanol ester on plasma cholesterol levels and red blood cell fragility in hamsters

The aim of this study was to assess the efficacy of a novel water-soluble phytostanol anolog, disodium ascorbyl phytostanyl phosphate (DAPP), on plasma lipid levels and red blood cell fragility in hamsters fed atherogenic diets. For 4 wk, 50 male Golden Syrian hamsters were fed a semipurified diet without added cholesterol (noncholesterol, group 1), or a semipurified diet with 0.25% cholesterol (cholesterol-control, group 2). Groups 3–5 were fed the cholesterol-control diet with an addition of 1% phytostanols (diet 3), 0.71% DAPP (DAPP 0.7%, diet 4), or 1.43% DAPP (DAPP 1.4%, diet 5). Diets 4 and 5 provided 0.5 and 1% phytostanols, respectively. Supplementation of 0.71 and 1.43% DAPP decreased plasma total cholesterol concentrations by 34 (P<0.001) and 46% (P<0.001), respectively, in comparison with the cholesterol-control group, whereas free stanols reduced (P=0.007) plasma cholesterol concentrations by 14%. Similarly, non-HDL-cholesterol concentrations were reduced by 39 (P<0.001) and 54% (P<0.001) in hamsters supplemented with DAPP 0.7% and DAPP 1.4%, respectively, relative to the cholesterol-control group. The hypocholesterolemic effect of DAPP 1.4% was threefold stronger than that of free stanols. In hamsters supplemented with DAPP 1.4%, plasma TG concentrations were 45% lower (P=0.018) than in cholesterol-control-fed hamsters, whereas no such beneficial effect was observed in the free stanol group. Erythrocyte fragility was unaffected by DAPP or free phytostanols. Results of the current study demonstrate that DAPP lowers cholesterol more efficiently than free stanols, without an adverse effect on erythrocyte fragility in hamsters.

Longer Term Effects of Early Cholesterol Intake on Cholesterol Biosynthesis and Plasma Lipids: A Randomized Clinical Trial

Abstract 25 Introduction 27 Materials and methods 30 Results 34 Discussion 36 Summary and conclusions 42 Tables and figures -45 References 55 Appendix 1 . Laboratory procedures 63 Appendix 2 . Compiled data 69 Appendix 3