ArticleNutrients2020
NPC1L1 Facilitates Sphingomyelin Absorption and Regulates Diet-Induced Production of VLDL/LDL-associated S1P.
Article in Nutrients, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Dual functions of NPC1L1 for cholesterol transport: Cholesterol capture and regulation of inner-leaflet cholesterol accessibility.iScience · 2026Article
- The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026Review
- Dietary phytosterols induce infertility in female mice via epigenomic modulations.Communications biology · 2024Article
- Lipid-lowering drugs affect lung cancer risk via sphingolipid metabolism: a drug-target Mendelian randomization study.Frontiers in genetics · 2023Article
- Emerging Evidence of Pathological Roles of Very-Low-Density Lipoprotein (VLDL).International journal of molecular sciences · 2022Review
- Factors Influencing Gallstone Formation: A Review of the Literature.Biomolecules · 2022Review
- Molecular cloning and characterization of NPC1L1 in the Chinese tree shrew (Tupaia belangeri chinensis).Molecular biology reports · 2021Article
- Digestion and Absorption of Milk Phospholipids in Newborns and Adults.Frontiers in nutrition · 2021Review
- The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Niemann-Pick C1-Like 1 (NPC1L1) is a cholesterol importer and target of ezetimibe, a cholesterol absorption inhibitor used clinically for dyslipidemia. Recent studies demonstrated that NPC1L1 regulates the intestinal absorption of several fat-soluble nutrients, in addition to cholesterol. The study was conducted to reveal new physiological roles of NPC1L1 by identifying novel dietary substrate(s). Very low-density lipoprotein and low-density lipoprotein (VLDL/LDL) are increased in Western diet (WD)-fed mice in an NPC1L1-dependent manner, so we comprehensively analyzed the NPC1L1-dependent VLDL/LDL components. Apolipoprotein M (apoM), a binding protein of sphingosine-1-phosphate (S1P: a lipid mediator), and S1P were NPC1L1-dependently increased in VLDL/LDL by WD feeding. S1P is metabolized from sphingomyelin (SM) and SM is abundant in WD, so we focused on intestinal SM absorption. In vivo studies with Npc1l1 knockout mice and in vitro studies with NPC1L1-overexpressing cells revealed that SM is a physiological substrate of NPC1L1. These results suggest a scenario in which dietary SM is absorbed by NPC1L1 in the intestine, followed by SM conversion to S1P and, after several steps, S1P is exported into the blood as the apoM-bound form in VLDL/LDL. Our findings provide insight into the functions of NPC1L1 for a better understanding of sphingolipids and S1P homeostasis.
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