Premium
The role of suppressor enhancer lin‐12 1 like (SEL1L) in cholesterol metabolism
Author(s) -
Krumm Christopher,
Francisco Adam,
Chang WeiHua,
Long Qiaoming
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1208.10
Subject(s) - endoplasmic reticulum , cholesterol , biology , fatty liver , liver disease , lipid metabolism , homeostasis , medicine , endocrinology , biochemistry , disease
Cholesterol is a physiologically essential sterol synthesized in the liver. Cholesterol homeostasis in the liver is regulated by a network of genes including those encoding catalytic enzymes and transcription factors. Suppressor Enhancer Lin‐12 1 Like (SEL1L) encodes an endoplasmic reticulum (ER) membrane protein that is highly expressed in the liver. To investigate the possible role of SEL1L in the regulation of cholesterol metabolism, we have developed a liver specific mouse model ( SEL1L LKO). SEL1L LKO mice show comparable body and liver growth to wild‐type mice on normal diet. When fed a high cholesterol/fat diet however, the body mass of the SEL1L LKO mice were significantly smaller than the controls, despite exhibiting a larger liver and gallbladder. Immunostaining analysis revealed an inflamed and damaged liver, which indicate the development of non‐alcoholic fatty liver disease and fibrosis. Furthermore, serum analysis revealed abnormally increased cholesterol and triglyceride levels. Immunoblotting analysis had shown down regulation of the previously mentioned rate limiting enzymes in the SEL1L LKO mice, which demonstrate the challenges in maintaining normal intracellular distributions. Therefore, our findings reveal implications that a liver‐specific knockout of SEL1L can lead to alterations in cholesterol metabolism, liver damage and disease.