Alteration of sphingolipid metabolism and pSTAT3 expression by dietary cholesterol in the gallbladder of hamsters

Hyun Woo Shin, Donghyun Kim, Yunsun Lee, Hwan Soo Yoo, Beom Jae Lee, Jae Seon Kim, Soyong Jang, Heena Lim, Yeonju Lee, Seikwan Oh

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Cholesterol and sphingolipids are major lipid constituents of the plasma membrane and have been implicated in a number of human diseases, such as atherosclerosis, fatty liver, diabetes mellitus, coronary heart disease, and hypertension. However, the relationship between cholesterol and sphingolipid metabolism has not been investigated. The purpose of this study was to determine whether dietary cholesterol would induce the alteration of sphingolipid metabolism in hamsters. Hypercholesterolemia was induced in hamsters by placing them on an experimental diet containing 0.5% cholesterol plus 0.5% choline chloride for 8 and 12 weeks. The serum profile of the hamsters showed that the administration of cholesterol increased the levels of total cholesterol, LDL cholesterol, and triglycerides as well as the activities of GOT and GPT. The levels of ceramide and sphingosine-1-phosphate (So-1-P) were remarkably elevated by 6-fold, respectively, in the bile juice of cholesterol-fed hamsters. Interestingly, the levels of iNOS and GFAP were increased in the gallbladders of cholesterol-fed hamsters. In addition, the immunostaining of pSTAT3 was increased on the gallbladder epithelium after cholesterol feeding. These results suggest that sphingolipid metabolism may be regulated in the bile juice during cholesterol feeding and may be a potential target for the treatment of hypercholesterolemia-induced diseases.

Original languageEnglish
Pages (from-to)1253-1262
Number of pages10
JournalArchives of Pharmacal Research
Volume32
Issue number9
DOIs
StatePublished - Sep 2009

Bibliographical note

Funding Information:
This work has been supported by a grant (20070301-034-026-007-04-00) from the BioGreen 21 Program, Rural Development Administration, Korea.

Keywords

  • Ceramide
  • Cholesterol
  • GFAP
  • Hamsters
  • Sphingosine-1-phosphate
  • STAT3

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