2012 Fiscal Year Final Research Report
Elucidation of the mechanism involved in energy metabolic regulation by heparan sulfate
| Project/Area Number |
22590296
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Aichi Medical University |
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Principal Investigator |
NAGAI Naoko 愛知医科大学, 分子医科学研究所, 助教 (00367799)
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| Co-Investigator(Kenkyū-buntansha) |
KIMATA Koji 愛知医科大学, 名誉教授 (10022641)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 糖鎖生物学 / 代謝 |
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| Research Abstract |
Heparan sulfate (HS) is a glycosaminoglycan chain which localizes extracellulary where it plays important roles in various biological processes. Heparan sulfate 6-O-sulfotransferase-2 (Hs6st2) is one of the enzymes that add sulfate groups to HS. Here we report that male Hs6st2 knockout mice showed reduced energy metabolism. Thus, 6-O-sulfation in HS seems to play an important role in mediating energy metabolism and alteration of the HS composition may result in metabolic syndrome phenotypes. Heparan sulfate 6-O-sulfation was reduced in brown adipose tissue, a major tissue regulating energy metabolism. When cultures of brown adipocytes from wild type and Hs6st2 knockout mice isolated and differentiated in vitro were treated with FGF21, downstream signaling was reduced. The serum level of thyroid stimulating hormone was significantly higher, and that of thyroxin was lower in the knockout mice, suggesting hypothyroid phenotype.
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