The low-density lipoprotein receptor contributes to carotenoid homeostasis by regulating tissue uptake and fecal elimination

Mol Metab. 2024 Oct:88:102007. doi: 10.1016/j.molmet.2024.102007. Epub 2024 Aug 10.

Abstract

Objective: Carotenoids are lipophilic plant molecules with antioxidant properties. Some carotenoids such as β-carotene also serve as vitamin A precursors, playing a key role in human health. Carotenoids are transported in lipoproteins with other lipids such as cholesterol, however, the mechanisms responsible for carotenoid storage in tissues and their non-enzymatic elimination remain relatively unexplored. The goal of this study was to examine the contribution of the low-density lipoprotein receptor (LDLR) in the bodily distribution and disposal of carotenoids.

Methods: We employed mice lacking one or both carotenoid-cleaving enzymes as suitable models for carotenoid accumulation. We examined the contribution of LDLR in carotenoid distribution by crossbreeding these mice with Ldlr-/- mice or overexpressing LDLR in the liver.

Results: Our results show that LDLR plays a dual role in carotenoid homeostasis by simultaneously favoring carotenoid storage in the liver and adipose tissue while facilitating their fecal elimination.

Conclusions: Our results highlight a novel role of the LDLR in carotenoid homeostasis, and unveil a previously unrecognized disposal pathway for these important bioactive molecules.

Keywords: Basolateral membrane; Enterocyte; Retinoids.

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Carotenoids* / metabolism
  • Feces* / chemistry
  • Female
  • Homeostasis*
  • Liver* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Mice, Knockout
  • Receptors, LDL* / metabolism

Substances

  • Carotenoids
  • Receptors, LDL
  • Ldlr protein, mouse