Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease[S]

Ines Magro dos Reis, Tom Houben, Yvonne Oligschlager, Leoni Bucken, Hellen Steinbusch, David Cassiman, Dieter Luetjohann, Marit Westerterp, Jos Prickaerts, Jogchum Plat, Ronit Shiri-Sverdlov*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

Abstract

Niemann-Pick type C (NPC)1 disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key factor in the development of atherosclerosis and NASH. In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH, and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring a Npc1-null allele (Npc1(nih)), creating a dysfunctional NPC1 protein. Npc1(nih) mice were fed a 2% or 6% plant stanol ester-enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1(nih) mice fed the plant stanol-enriched diet exhibited lower hepatic cholesterol accumulation, damage, and inflammation than regular chow-fed Npc1(nih) mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular toward an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease.

Original languageEnglish
Pages (from-to)830-839
Number of pages10
JournalJournal of Lipid Research
Volume61
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • inflammation
  • cholesterol metabolism
  • diet
  • dietary lipids
  • liver
  • atherosclerosis
  • nonalcoholic steatohepatitis
  • lysosomal storage disease
  • DISEASE TYPE-C
  • LOW-DENSITY-LIPOPROTEIN
  • CHOLESTEROL-METABOLISM
  • PLASMA-CHOLESTEROL
  • STEROLS
  • INFLAMMATION
  • THERAPY
  • STATIN
  • ATHEROSCLEROSIS
  • PHYTOSTANOLS

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