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CLINICAL RESEARCH

Consumption of Saturated Fat Impairs the Anti-Inflammatory Properties of High-Density Lipoproteins and Endothelial Function

Stephen J. Nicholls, MBBS, PhD, FRACP, FACC^_*,, Pia Lundman, MD, PhD, FESC^_*,,, Jason A. Harmer, BSc (Hons), Belinda Cutri, BMedSc (Hons)^_*, Kaye A. Griffiths, DMU, Kerry-Anne Rye, PhD^_*, Philip J. Barter, MBBS, PhD, FRACP^_*,|| and David S. Celermajer, MBBS, PhD, FRACP^_*,,||,_*

^_* The Heart Research Institute, Sydney, Australia
Department of Medicine, University of Adelaide, Adelaide, Australia
Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia
Division of Medicine, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden
^|| Department of Medicine, University of Sydney, Sydney, Australia

Manuscript received November 23, 2005; revised manuscript received April 13, 2006, accepted April 18, 2006.

^_* Reprint requests and correspondence: Prof. David Celermajer, Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. (Email: david.celermajer{at}email.cs.nsw.gov.au).

OBJECTIVES: The purpose of this study was to investigate the influence of dietary fatty acids on the anti-inflammatory properties of high-density lipoproteins (HDL) and vascular function.

BACKGROUND: The effect of dietary fatty acids on atherogenesis remains uncertain.

METHODS: Fourteen adults consumed an isocaloric meal containing either a polyunsaturated or a saturated fat on 2 occasions. The effects of post-prandial HDL on endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined. Flow-mediated dilation (FMD) and microvascular reactivity were assessed before and 3 and 6 h after the meal.

RESULTS: Plasma triglycerides, insulin, and nonesterified fatty acids rose after the meals. The HDL collected 6 h after the saturated meal were less effective than HDL isolated from fasting plasma in terms of their ability to inhibit expression of ICAM-1 and VCAM-1, whereas HDL collected 6 h after the polyunsaturated meal had an inhibitory activity that was greater than that of HDL collected from fasting plasma (p < 0.004 and p = 0.01 for comparison of effect of meals on ICAM-1 and VCAM-1, respectively). Post-hyperemic microvascular flow significantly increased at 3 h after the polyunsaturated meal by 45 ± 14% and by 21 ± 11% after the saturated meal. The FMD decreased 3 h after the saturated meal by 2.2 ± 0.9% (p < 0.05 compared with baseline) and by 0.9 ± 1% after the polyunsaturated meal.

CONCLUSIONS: Consumption of a saturated fat reduces the anti-inflammatory potential of HDL and impairs arterial endothelial function. In contrast, the anti-inflammatory activity of HDL improves after consumption of polyunsaturated fat. These findings highlight novel mechanisms by which different dietary fatty acids may influence key atherogenic processes.

Abbreviations and Acronyms   apoA-I = apolipoprotein A-I   FMD = flow-mediated dilation   HDL = high-density lipoprotein   ICAM-1 = intercellular adhesion molecule 1   VCAM-1 = vascular cell adhesion molecule 1

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