Alteration of sphingolipid metabolism and pSTAT3 expression by dietary cholesterol in the gallbladder of hamsters.
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.
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Hyun-Woo
HW
Shin
Donghyun
D
Kim
Yunsun
Y
Lee
Hwan-Soo
HS
Yoo
Beom Jae
BJ
Lee
Jae Seon
JS
Kim
Soyong
S
Jang
Heena
H
Lim
Yeonju
Y
Lee
Seikwan
S
Oh
D000818:Animals; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D006224:Cricetinae; D005704:Gallbladder / Q000378:metabolism*; D042882:Gallstones / Q000209:etiology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D008297:Male; D008647:Mesocricetus; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism*
D002791:Cholesterol, Dietary; D005904:Glial Fibrillary Acidic Protein; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D013107:Sphingolipids; D052247:Nitric Oxide Synthase Type II