Controversy over the atherogenicity of lipoprotein-X

Curr Opin Endocrinol Diabetes Obes. 2019 Apr;26(2):117-123. doi: 10.1097/MED.0000000000000466.

Abstract

Purpose of review: Lipoprotein-X (Lp-X) is an abnormal lipoprotein containing abundant free cholesterol and phospholipids, as well as some apolipoprotein E (apoE). Serum Lp-X increases in patients with cholestasis and lecithin-cholesterol acyltransferase deficiency, as well as in those receiving intravenous lipid emulsion. Lp-X is often associated with skin xanthomas in cholestatic patients. However, earlier studies showed that Lp-X is not taken up by murine macrophages, but exerts antiatherogenic actions. In this review, we discuss the heterogeneity of Lp-X and its potential atherogenicity.

Recent findings: Mass spectrometry revealed that Lp-X of cholestatic patients is similar in lipid composition to low-density lipoprotein (LDL) and high-density lipoprotein, but not to bile acids, suggesting that Lp-X is synthesized in the liver. Palmar xanthomas appear in patients with cholestasis, but regress over months after improvement of hypercholesterolemia. Lp-X isolated from cholestatic patients is rich in apoE, and causes more lipid accumulation than oxidized LDL and acetyl LDL in human monocyte-derived macrophages.

Summary: Lp-X is heterogeneous in apoE content. Lp-X is taken up in cholestatic patients by apoE-recognizing lipoprotein receptors. Further research is warranted to fully understand the atherogenicity of Lp-X and the clinical significance of elevated Lp-X concentrations, particularly in cholestatic patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Atherosclerosis / etiology*
  • Atherosclerosis / metabolism
  • Cholestasis / metabolism
  • Humans
  • Lipoprotein-X / metabolism
  • Lipoprotein-X / toxicity*
  • Macrophages / metabolism

Substances

  • Lipoprotein-X