Department of Food Science and Human Nutrition, University of Illinois Urbana Champaign, Urbana, IL, USA.
Department of Food Science and Human Nutrition, University of Illinois Urbana Champaign, Urbana, IL, USA; Division of Nutritional Sciences, University of Illinois Urbana Champaign, Urbana, IL, USA.
Mol Metab. 2024 Oct;88:102007. doi: 10.1016/j.molmet.2024.102007. Epub 2024 Aug 10.
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.
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.
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.
Our results highlight a novel role of the LDLR in carotenoid homeostasis, and unveil a previously unrecognized disposal pathway for these important bioactive molecules.
类胡萝卜素是具有抗氧化特性的亲脂性植物分子。一些类胡萝卜素，如β-胡萝卜素，也作为维生素 A 的前体，在人类健康中起着关键作用。类胡萝卜素与胆固醇等其他脂质一起在脂蛋白中运输，然而，负责类胡萝卜素在组织中的储存和非酶促消除的机制仍相对未知。本研究的目的是研究低密度脂蛋白受体（LDLR）在类胡萝卜素的体内分布和处置中的作用。
我们使用缺乏一种或两种类胡萝卜素裂解酶的小鼠作为类胡萝卜素积累的合适模型。我们通过将这些小鼠与 Ldlr-/- 小鼠杂交或在肝脏中过表达 LDLR，来研究 LDLR 在类胡萝卜素分布中的作用。
我们的结果表明，LDLR 通过同时促进肝脏和脂肪组织中类胡萝卜素的储存，同时促进其粪便排泄，在类胡萝卜素的动态平衡中发挥双重作用。
我们的结果强调了 LDLR 在类胡萝卜素动态平衡中的新作用，并揭示了这些重要生物活性分子的先前未被认识的处置途径。
