title: Alkaline sphingomyelinase (NPP7) promotes cholesterol absorption by affecting sphingomyelin levels in the gut: A study with NPP7 knockout mice.
abstract: We previously showed that dietary sphingomyelin (SM) inhibited cholesterol absorption in animals. The key enzyme hydrolyzing SM in the gut is alkaline sphingomyelinase (alk-SMase, nucleotide pyrophosphatase/phosphodiesterase 7). Here using the fecal dual-isotope ratio method we compared cholesterol absorption in the wild-type (WT) and alk-SMase knockout (KO) mice. The animals were fed an emulsion containing [(14)C]cholesterol and [(3)H]sitosterol. The radioactivities in the lipids of the fecal samples collected 4, 8, and 24 h thereafter were determined, and the ratio of (14)C/(3)H was calculated. We found that the fecal [(14)C]cholesterol recovery in the KO mice was significantly higher than in the WT mice. A maximal 92% increase occurred 8 h after feeding. Recovery of [(3)H]sitosterol did not differ between the two groups. Accordingly, the (14)C-to-(3)H ratio of fecal lipids was 133% higher at 8 h and 75% higher at 24 h in the KO than in the WT mice. Decreased [(14)C]cholesterol was also found in the serum of the KO mice 4 h after feeding. Supplement of SM in the emulsion reduced the differences in fecal [(14)C]cholesterol recovery between the WT and KO mice because of a greater increase of [(14)C]cholesterol recovery in the WT mice. Without treatment, the KO mice had significantly higher SM levels in the intestinal content and feces, but not in the intestinal mucosa or serum. The expression of Niemann-Pick C1 like 1 protein in the small intestine was not changed. In conclusion, alk-SMase is a physiological factor promoting cholesterol absorption by reducing SM levels in the intestinal lumen.
authors.affiliation: Gastroenterology and Nutrition Lab, Institution of Clinical Sciences, University of Lund, Lund, Sweden; Daqing Campus, Harbin Medical University, Daqing, China;
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Gastroenterology and Nutrition Lab, Institution of Clinical Sciences, University of Lund, Lund, Sweden; Gastroenterology, Tongji Hospital, Tongji University, Shanghai, China; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Gastroenterology and Nutrition Lab, Institution of Clinical Sciences, University of Lund, Lund, Sweden;
authors.forename: Yajun
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Gastroenterology Clinic, Skåne University Hospital, Lund, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Hertervig
authors.affiliation: Gastroenterology and Nutrition Lab, Institution of Clinical Sciences, University of Lund, Lund, Sweden;
authors.forename: Lena
authors.initials: L
authors.lastname: Ohlsson
authors.affiliation: Gastroenterology and Nutrition Lab, Institution of Clinical Sciences, University of Lund, Lund, Sweden; Gastroenterology Clinic, Skåne University Hospital, Lund, Sweden.
authors.forename: Ake
authors.initials: A
authors.lastname: Nilsson
authors.affiliation: Gastroenterology and Nutrition Lab, Institution of Clinical Sciences, University of Lund, Lund, Sweden; Rui-dong.duan@med.lu.se.
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Duan
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D012855:Sitosterols / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000502:physiology*; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D026901:Membrane Transport Proteins; C482445:Npc1l1 protein, mouse; D012855:Sitosterols; D013109:Sphingomyelins; C025473:gamma-sitosterol; D002784:Cholesterol; D013108:Sphingomyelin Phosphodiesterase
keywords: Niemann-Pick C1 like 1 protein; cholesterol; nucleotide pyrophosphatase/phosphodiesterase