Walnut oil increases cholesterol efflux through inhibition of stearoyl CoA desaturase 1 in THP-1 macrophage-derived foam cells

Jun Zhang,Penny M Kris-Etherton,Jessica A Grieger,Jennifer A Fleming,Jerry T Thompson,Peter J Gillies,John P Vanden Heuvel

doi:10.1186/1743-7075-8-61

Abstract

BackgroundWalnuts significantly decrease total and low-density lipoprotein cholesterol in normo- and hypercholesterolemic individuals. No study to date has evaluated the effects of walnuts on cholesterol efflux, the initial step in reverse cholesterol transport, in macrophage-derived foam cells (MDFC). The present study was conducted to investigate the mechanisms by which walnut oil affects cholesterol efflux.MethodsThe extract of English walnuts (walnut oil) was dissolved in DMSO and applied to cultured THP-1 MDFC cells (0.5 mg/mL). THP-1 MDFC also were treated with human sera (10%, v:v) taken from subjects in a walnut feeding study. Cholesterol efflux was examined by liquid scintillation counting. Changes in gene expression were quantified by real time PCR.ResultsWalnut oil treatment significantly increased cholesterol efflux through decreasing the expression of the lipogenic enzyme stearoyl CoA desaturase 1 (SCD1) in MDFC. Alpha-linolenic acid (ALA), the major n-3 polyunsaturated fatty acids found in walnuts, recaptured SCD1 reduction in MDFC, a mechanism mediated through activation of nuclear receptor farnesoid-X-receptor (FXR). Postprandial serum treatment also increased cholesterol efflux in MDFC. When categorized by baseline C-reactive protein (CRP; cut point of 2 mg/L), subjects in the lower CRP sub-group benefited more from dietary intervention, including a more increase in cholesterol efflux, a greater reduction in SCD1, and a blunted postprandial lipemia.ConclusionIn conclusion, walnut oil contains bioactive molecules that significantly improve cholesterol efflux in MDFC. However, the beneficial effects of walnut intake may be reduced by the presence of a pro-inflammatory state.Trial RegistrationClinicalTrials.gov: NCT00938340

Highlights

Walnuts significantly decrease total and low-density lipoprotein cholesterol in normo- and hypercholesterolemic individuals
Walnut oil increases cholesterol efflux and reduces stearoyl CoA desaturase 1 (SCD1) expression in THP-1 macrophage-derived foam cells (MDFC) Following walnut oil treatment (0.5 mg/mL), cholesterol efflux was significantly increased by 35%, compared to DMSO control treatment (Figure 1A)
Among the key enzymes tested in the lipid synthesis (FAS, ACC, HMGCR, ELOVL6) and oxidation (CPT, ACO) pathways, only SCD1 mRNA was significantly reduced in a dose-dependent manner following walnut oil treatment (Figure 1C)

Summary

Introduction

Walnuts significantly decrease total and low-density lipoprotein cholesterol in normo- and hypercholesterolemic individuals. To stabilize the arterial plaque and prevent cardiac events, it is critically important to alleviate the peripheral lipid burden. This can be achieved by lowering de novo lipogenesis and/or increasing the capacity of Numerous studies have shown that nut consumption favorably affects circulating lipids and lipoproteins with LDL-cholesterol (LDL-C) being reduced by 3% to 19% in different populations [1]. The hypocholesterolemic effects of walnuts are attributed to decreased de novo lipogenesis due to their high PUFA content [3]. Walnut PUFA would be predicted to lower the cholesterol burden in atherosclerotic plaques. No study to date has evaluated the effects of walnuts on cholesterol efflux

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