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Open Access Research

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

Jun Zhang12, Jessica A Grieger1, Penny M Kris-Etherton12, Jerry T Thompson3, Peter J Gillies4, Jennifer A Fleming1 and John P Vanden Heuvel123*

Author Affiliations

1 Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, 16802, USA

2 Center of Excellence in Nutrigenomics, The Pennsylvania State University, University Park, PA, 16802, USA

3 Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA

4 Department of Nutritional Sciences, Institute for Food, Nutrition and Health, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA

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Nutrition & Metabolism 2011, 8:61  doi:10.1186/1743-7075-8-61

Published: 26 August 2011

Abstract

Background

Walnuts 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.

Methods

The 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.

Results

Walnut 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.

Conclusion

In 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 Registration

ClinicalTrials.gov: NCT00938340

Keywords:
cholesterol efflux; CRP; FXR; SCD1; walnut oil