Cytosolic
sulfotransferase (SULT2B1b) catalyzes
oxysterol sulfation. 5-Cholesten-3β-25-diol-3-sulfate (
25HC3S), one product of this reaction, decreases intracellular
lipids in vitro by suppressing
liver X receptor/
sterol regulatory element binding protein (SREBP)-1c signaling, with regulatory properties opposite to those of its precursor
25-hydroxycholesterol. Upregulation of SULT2B1b may be an effective strategy to treat
hyperlipidemia and hepatic steatosis. The objective of the study was to explore the effect and mechanism of
oxysterol sulfation by SULT2B1b on lipid metabolism in vivo. C57BL/6 and LDLR(-/-) mice were fed with high-
cholesterol diet or high-fat diet for 10 weeks and infected with adenovirus encoding SULT2B1b. SULT2B1b expressions in different tissues were determined by immunohistochemistry and Western blot. Sulfated
oxysterols in liver were analyzed by high-pressure liquid chromatography. Serum and hepatic
lipid levels were determined by kit
reagents and
hematoxylin and
eosin staining. Gene expressions were determined by real-time
reverse transcriptase polymerase chain reaction and Western Blot. Following
infection, SULT2B1b was successfully overexpressed in the liver, aorta, and lung tissues, but not in the heart or kidney. SULT2B1b overexpression, combined with administration of
25-hydroxycholesterol, significantly increased the formation of
25HC3S in liver tissue and significantly decreased serum and hepatic
lipid levels, including
triglycerides, total
cholesterol, free
cholesterol, and
free fatty acids, as compared with controls in both C57BL/6 and LDLR(-/-) mice. Gene expression analysis showed that increases in SULT2B1b expression were accompanied by reduction in key regulators and
enzymes involved in lipid metabolism, including
liver X receptor α, SREBP-1, SREBP-2,
acetyl-CoA carboxylase-1, and
fatty acid synthase. These findings support the hypothesis that
25HC3S is an important endogenous regulator of
lipid biosynthesis.