Hyperalphalipoproteinemic scavenger receptor BI knockout mice exhibit a disrupted epidermal lipid barrier

https://doi.org/10.1016/j.bbalip.2019.158592Get rights and content
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Highlights

  • SR-BI deficiency causes hyperalphalipoproteinemia but preserves skin morphology.

  • SR-BI/ epidermis is enriched with unsaturated free fatty acid (FFA) species.

  • Plasma levels of cholesteryl esters correlate with epidermal FFA C18:1 content.

  • Cholesterol and fatty acid synthesis genes are downregulated in the SR-BI/ skin.

  • Epidermal unsaturated/short fatty acids in SR-BI/ mice reduce lipid barrier.

Abstract

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters (CE) from high-density lipoproteins (HDL). An impaired SR-BI function leads to hyperalphalipoproteinemia with elevated levels of cholesterol transported in the HDL fraction. Accumulation of cholesterol in apolipoprotein B (apoB)-containing lipoproteins has been shown to alter skin lipid composition and barrier function in mice. To investigate whether these hypercholesterolemic effects on the skin also occur in hyperalphalipoproteinemia, we compared skins of wild-type and SR-BI knockout (SR-BI/) mice. SR-BI deficiency did not affect the epidermal cholesterol content and induced only minor changes in the ceramide subclasses. The epidermal free fatty acid (FFA) pool was, however, enriched in short and unsaturated chains. Plasma CE levels strongly correlated with epidermal FFA C18:1 content. The increase in epidermal FFA coincided with downregulation of cholesterol and FFA synthesis genes, suggesting a compensatory response to increased flux of plasma cholesterol and FFAs into the skin. Importantly, the SR-BI/ epidermal lipid barrier showed increased permeability to ethyl-paraminobenzoic acid, indicating an impairment of the barrier function. In conclusion, increased HDL-cholesterol levels in SR-BI/ mice can alter the epidermal lipid composition and lipid barrier function similarly as observed in hypercholesterolemia due to elevated levels of apoB-containing lipoproteins.

Abbreviations

APCI
Atmospheric pressure chemical ionication
apoB
apolipoprotein B
apoE
apolipoprotein E
AUC
area under the curve
CER
ceramide
CE
cholesteryl ester
E-PABA
ethyl-paraminobenzoic acid
FC
free cholesterol
(F)FA
(free) fatty acid
FTIR
Fourier transform infrared spectroscopy
HDL
high-density lipoprotein
LCAT
lecithin: cholesterol acyl transferase
(V)LDL
(very)low-density lipoprotein
(m)LMM
(murine) lipid model membrane
PBS
phosphate buffer saline
SC
stratum corneum
SR-BI
scavenger receptor class B type I
WT
wild-type

Keywords

High-density lipoprotein
Hypercholesterolemia
Hyperlipidemia
Cholesteryl esters
Epidermis
Skin lipid metabolism
Free fatty acids

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1

Both authors contributed equally.