In vitro regulation of low-density lipoprotein receptor interaction by fatty acids

Hannah, Judy S.; Yamane, Kiminori; Berlin, Elliott; Howard, Barbara V.

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Volume 44, Issue 11 , Pages 1428-1434, November 1995

In vitro regulation of low-density lipoprotein receptor interaction by fatty acids☆

Judy S. Hannah
- Address reprint requests to Judy S. Hannah, PhD, Research Scientist, Medlantic Research Institute, 108 Irving St NW, Washington, DC 20010.
- Medlantic Research Institute, Washington, DC, USA
- Beltsville Human Nutrition Research Center, US Department of Agriculture, Beltsville, MD, USA
Kiminori Yamane
- Medlantic Research Institute, Washington, DC, USA
- Beltsville Human Nutrition Research Center, US Department of Agriculture, Beltsville, MD, USA
Elliott Berlin
- Medlantic Research Institute, Washington, DC, USA
- Beltsville Human Nutrition Research Center, US Department of Agriculture, Beltsville, MD, USA
Barbara V. Howard
- Medlantic Research Institute, Washington, DC, USA
- Beltsville Human Nutrition Research Center, US Department of Agriculture, Beltsville, MD, USA

Received 10 September 1994; accepted 9 March 1995.

Abstract

Low-density lipoprotein (LDL) receptor binding is the initial step in receptor-mediated clearance. Dietary fat composition is known to affect LDL clearance, but the mechanism of the effect is unknown. We have examined the effects of altered membrane fatty acid composition, as might occur when specific dietary fats are consumed, on LDL binding using a Chinese hamster ovary (CHO) line that constitutively expresses the human LDL receptor. Binding of pooled human LDL to its receptor was compared in cells enriched with various fatty acids. Binding affinity was greater (lower K_d) for cells grown in 16:0-, 18:0-, or 18:1-enriched media than for those grown in 18:2 (P < .0001). The apparent receptor number (Bmax) was lower for cells enriched in saturated fatty acids and 18:1. Fluidity was assessed by measuring diphenylhexatriene (DPH) fluorescence anisotropy (r_s). Cells enriched in 18:1 or 18:2 were the most fluid (P < .003). The correlation between binding and fluidity (r = .24, P = .27) was weak and did not appear to explain the effects of fatty acid modification on LDL receptor binding. Thus, it appears that cellular enrichment in 16:0, 18:0, and 18:1 increases binding affinity by affecting properties other than membrane fluidity. Changes in Bmax may also contribute to the observed differences in LDL binding.

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