title: Cholesteryl ester accumulation and accelerated cholesterol absorption in intestine-specific hormone sensitive lipase-null mice.
abstract: Hormone sensitive lipase (HSL) regulates the hydrolysis of acylglycerols and cholesteryl esters (CE) in various cells and organs, including enterocytes of the small intestine. The physiological role of this enzyme in enterocytes, however, stayed elusive. In the present study we generated mice lacking HSL exclusively in the small intestine (HSLiKO) to investigate the impact of HSL deficiency on intestinal lipid metabolism and the consequences on whole body lipid homeostasis. Chow diet-fed HSLiKO mice showed unchanged plasma lipid concentrations. In addition, feeding with high fat/high cholesterol (HF/HC) diet led to unaltered triglyceride but increased plasma cholesterol concentrations and CE accumulation in the small intestine. The same effect was observed after an acute cholesterol load. Gavaging of radioactively labeled cholesterol resulted in increased abundance of radioactivity in plasma, liver and small intestine of HSLiKO mice 4h post-gavaging. However, cholesterol absorption determined by the fecal dual-isotope ratio method revealed no significant difference, suggesting that HSLiKO mice take up the same amount of cholesterol but in an accelerated manner. mRNA expression levels of genes involved in intestinal cholesterol transport and esterification were unchanged but we observed downregulation of HMG-CoA reductase and synthase and consequently less intestinal cholesterol biosynthesis. Taken together our study demonstrates that the lack of intestinal HSL leads to CE accumulation in the small intestine, accelerated cholesterol absorption and decreased cholesterol biosynthesis, indicating that HSL plays an important role in intestinal cholesterol homeostasis.
authors: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria.
authors: Sascha
authors: S
authors: Obrowsky
authors: Prakash G
authors: PG
authors: Chandak
authors: Jay V
authors: JV
authors: Patankar
authors: Thomas
authors: T
authors: Pfeifer
authors: Silvia
authors: S
authors: Povoden
authors: Renate
authors: R
authors: Schreiber
authors: Guenter
authors: G
authors: Haemmerle
authors: Sanja
authors: S
authors: Levak-Frank
authors: Dagmar
authors: D
authors: Kratky
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D005260:Female; D019426:Integrases / Q000378:metabolism; D007408:Intestinal Absorption; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002787:Sterol Esterase / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D008055:Lipids; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; C045073:Cre recombinase; D019426:Integrases; D002787:Sterol Esterase