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Hepatic SCD1 deficiency does not protect against plasma and hepatic lipid accumulation associated with T0901317‐mediated LXR activation
Author(s) -
Chu Kiki,
Ntambi James M
Publication year - 2007
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.21.5.a605-c
Subject(s) - liver x receptor , hypertriglyceridemia , medicine , endocrinology , triglyceride , chemistry , cholesterol , fatty liver , lipid metabolism , biology , biochemistry , nuclear receptor , transcription factor , gene , disease
Stearoyl‐coenzyme A desaturase (SCD) is the rate‐limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. Studies with global SCD1 deficient mice have provided evidence that SCD1 plays an important role in lipid homeostasis and lipoprotein metabolism. Previously, we have found that global SCD1 deficiency protects against hypertriglyceridemia, reduces hepatic triglyceride accumulation, and increases plasma high‐density lipoprotein (HDL) cholesterol upon T0901317‐mediated liver X receptor (LXR) activation. In this study, we investigated the effect of T0901317‐mediated LXR activation on liver‐specific SCD1 knockout (LSCD1KO) mice. Upon 2‐day treatment of T0901317, LSCD1KO mice exhibited increase in plasma triglyceride levels to the same extent as SCD1flox/flox control counterparts. Plasma HDL‐cholesterol level was also elevated in LSCD1KO mice but was to the same level as SCD1flox/flox counterparts. Similarly, hepatic triglyceride accumulation upon T0901317 treatment was comparable in both SCD1flox/flox and LSCD1KO mice, exhibiting a similar fatty acid profile. Together, these results indicate that liver SCD1 deficiency alone is insufficient to protect mice against hypertriglyceridemia and hepatic lipid accumulation and promote HDL‐cholesterol elevation upon LXR activation, suggesting the beneficial effects seen in the global SCD1 deficiency upon LXR activation involve loss of SCD1 activity in extrahepatic tissues.