Advanced

Alkaline sphingomyelinase (NPP7) promotes cholesterol absorption by affecting sphingomyelin levels in the gut. A study with NPP7 knockout mice.

Zhang, Ping LU ; Chen, Ying LU ; Cheng, Yajun LU ; Hertervig, Erik LU ; Ohlsson, Lena LU ; Nilsson, Åke LU and Duan, Rui-Dong LU (2014) In American Journal of Physiology: Gastrointestinal and Liver Physiology 306(10). p.903-908
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, NPP7). Here using 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 calculated. We found that the fecal (14)C-cholesterol recovery in the KO mice was significantly higher than in the WT mice. Maximal 92% increase occurred 8 h after feeding. Recovery of (3)H-sitosterol did not... (More)
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, NPP7). Here using 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 calculated. We found that the fecal (14)C-cholesterol recovery in the KO mice was significantly higher than in the WT mice. Maximal 92% increase occurred 8 h after feeding. Recovery of (3)H-sitosterol did not differ between the two groups. Accordingly the (14)C/(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 due to 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 NPC1L1 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Gastrointestinal and Liver Physiology
volume
306
issue
10
pages
903 - 908
publisher
American Physiological Society
external identifiers
  • pmid:24650549
  • wos:000336844200010
  • scopus:84900822396
ISSN
1522-1547
DOI
10.1152/ajpgi.00319.2013
language
English
LU publication?
yes
id
a4c7a6c5-58b3-4d1d-8d14-9520e864c08b (old id 4382949)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24650549?dopt=Abstract
date added to LUP
2014-04-03 20:29:20
date last changed
2017-07-23 03:00:27
@article{a4c7a6c5-58b3-4d1d-8d14-9520e864c08b,
  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, NPP7). Here using 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 calculated. We found that the fecal (14)C-cholesterol recovery in the KO mice was significantly higher than in the WT mice. Maximal 92% increase occurred 8 h after feeding. Recovery of (3)H-sitosterol did not differ between the two groups. Accordingly the (14)C/(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 due to 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 NPC1L1 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.},
  author       = {Zhang, Ping and Chen, Ying and Cheng, Yajun and Hertervig, Erik and Ohlsson, Lena and Nilsson, Åke and Duan, Rui-Dong},
  issn         = {1522-1547},
  language     = {eng},
  number       = {10},
  pages        = {903--908},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Gastrointestinal and Liver Physiology},
  title        = {Alkaline sphingomyelinase (NPP7) promotes cholesterol absorption by affecting sphingomyelin levels in the gut. A study with NPP7 knockout mice.},
  url          = {http://dx.doi.org/10.1152/ajpgi.00319.2013},
  volume       = {306},
  year         = {2014},
}