アクティブボード・２０１１年　４月
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研究発表を行った学会；
・第３３回日本分子生物学会年会　
　２０１０年１２月７日〜１０日（神戸）

タイトル；Angptl6/AGF Regulates Energy Metabolism in a Manner Independent of its Proangiogenic Function.
　
発表者；　宮田　敬士　氏
　　　（熊本大学　大学院生命科学研究部　免疫・アレルギー・血管病態学寄附講座）

Abstract；
We have reported that AGF/Angptl6 counteracts obesity through increasing energy expenditure. Furthermore, AGF promotes in vivo angiogenesis through activating ERK-eNOS signaling pathway. It is well known that microvasculature in peripheral tissues assist in heat dissipation, resulting increases in energy expenditure. In this study, we examined whether AGF-induced microvasculature is essential for the effects of AGF on increasing energy expenditure. We generated transgenic eNOS null mice expressing AGF in keratinocytes (Tg) to investigate whether AGF directly affects energy metabolism without activating AGF-ERK-eNOS-NO angiogenesis pathway.Though eNOS-/- mice developed mild obesity on the normal chow diet, the body weight of Tg mice was suppressed compared with that of eNOS-/- mice due to a significant reduction in WAT and skeletal muscle weight per body weight. Furthermore, Tg mice exhibited a significant increase in whole body oxygen consumption rate compared with eNOS-/- mice. To determine the molecular basis of these metabolic changes in Tg mice, we investigated the expression levels of energy expenditure-related metabolic genes. The expression level in UCP2, UCP3 and PGC- 1β in skeletal muscle and PGC-1α, PGC-1β, PPARα and PPARδ in BAT in Tg mice were significant increase compared to those in eNOS-/- mice. There was no difference in vasculature between two groups. These current findings suggest that AGF regulates energy metabolism in a manner independent of its proangiogenic function, and that enhancing AGF signaling might constitute a new clinical strategy to counteract obesity through both direct and angiogenesis-mediated indirect on energy expenditure.