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25‐Hydroxycholesterol sulfation regulates lipid metabolism in vivo in mice
Author(s) -
Ren Shunlin,
Bai Qianming,
Xu Leyuan,
Pandak William M
Publication year - 2011
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.25.1_supplement.lb121
Subject(s) - oxysterol , lipid metabolism , sulfation , sterol regulatory element binding protein , cholesterol , chemistry , liver x receptor , abca1 , biochemistry , medicine , fatty acid synthase , endocrinology , biology , sterol , transcription factor , nuclear receptor , transporter , gene
Background Oxysterol sulfotransferase, SULT2B1b, catalyzes sulfation of 25‐hydroxycholesterol (25HC). The product 25‐hydroxycholesterol‐3‐sulfate (25HC3S) was found to decrease cellular lipids in human aortic endothelial cells, macrophages, and hepatocytes via inactivation of LXR/SREBP‐1c signaling. 25HC3S appears to be a potent regulator of lipid metabolism with regulatory properties opposite to those of its precursor 25‐HC. Hypothesis Oxysterol sulfation, by determining the balance between 25HC and 25HC3S, could play an important role in lipid homeostasis. Results Following transfection, the SULT2B1b gene was successfully overexpressed in liver, aorta and lung tissues, but not in heart or kidney. SULT2B1b overexpression significantly decreased hepatic triglycerides by 30%, total cholesterol by 28%, and free cholesterol by 18%, as compared to control, while fatty acids were unchanged. Gene expression analysis showed that increases in SULT2B1b expression were accompanied by reduction in key regulators and enzymes in lipid metabolism, including SREBP‐1, SREBP‐2, acetyl‐CoA carboxylase‐1 and fatty acid synthase. Conclusion Overexpression of SULT2B1b, accompanied by 25HC administration, suppresses SREBP‐1 and ‐2 and decreases serum and hepatic lipids in cholesterol‐fed mice. This finding supports the hypothesis that 25HC3S is an important endogenous regulator of lipid biosynthesis. This pathway may represent a novel target for pharmacological intervention in NAFLD.