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

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.

Bioactive sphingolipids in the biliary tract: Relevance for cholesterol gallstone disease

“…Therefore, one possible mechanism involves downregulation of inflammatory mediators in the gallbladder by inhibition of the de novo sphingolipid biosynthetic pathway. This scenario is supported by the findings of a previous study by the same group 14 . A high‐cholesterol diet fed to Syrian Golden hamsters induced gallstones in association with sixfold elevations of biliary ceramide and S1P.…”

The dietary ingredient, genistein, stimulates cathelicidin antimicrobial peptide expression through a novel S1P-dependent mechanism

“…S1P was derivatized with o-phthalaldehyde (OPA) reagent and then quantitated using an HPLC system equipped with a fluorometrical detector system (JASCO, Tokyo, Japan), as described previously [23]. S1P levels were expressed as pmol per mg protein.…”

An Endoplasmic Reticulum Stress-Initiated Sphingolipid Metabolite, Ceramide-1-Phosphate, Regulates Epithelial Innate Immunity by Stimulating β-Defensin Production

“…To assess the levels of cellular C1P, KC were incubated with Tg or C2Cer and washed with phosphate-buffered saline followed by extraction of total C1P, as we reported previously (30). C1P was derivatized with o-phthalaldehyde reagent and then quantitated using a high-performance liquid chromatography (HPLC) system equipped with a fluorometric detector system (JASCO, Tokyo, Japan), as described previously (30).…”