세부과제번호
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2017M3A9D5A01052447
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단계
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2단계 2차년도
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세부과제명
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유전자변형마우스의 노화 표현형 분석 파이프라인 구축과제
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공동 유/무
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N
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SCI여부
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Y
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게재년월
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-
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논문제목
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Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis.
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총저자명
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Hye-Sook Han, Byeong Hun Choi, Jun Seok Kim, Geon Kang, Seung-Hoi Koo
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학술지명
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Nat Commun
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게재권(호)
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8(1)
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저널구분
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-
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페이지수
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1878
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참여연구원
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-
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연구책임자
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구승회
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과제기여도
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30
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PMID
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29192248
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사사기관수
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-
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IF (년도)
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12.124
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제1저자
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Hye-Sook Han
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교신저자
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Seung-Hoi Koo
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공동저자
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Byeong Hun Choi, Jun Seok Kim, Geon Kang
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|
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초록
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Liver plays a crucial role in controlling energy homeostasis in mammals, although the exact mechanism by which it influences other peripheral tissues has yet to be addressed. Here we show that Creb regulates transcriptional co-activator (Crtc) 2 is a major regulator of whole-body energy metabolism. Crtc2 liver-specific knockout lowers blood glucose levels with improved glucose and insulin tolerance. Liver-specific knockout mice display increased energy expenditure with smaller lipid droplets in adipose depots. Both plasma and hepatic Fgf21 levels are increased in Crtc2 liver-specific knockout mice, as a result of the reduced miR-34a expression regulated by Creb/Crtc2 and the induction of Sirt1 and Pparα. Ectopic expression of miR-34a reverses the metabolic changes in knockout liver. We suggest that Creb/Crtc2 negatively regulates the Sirt1/Pparα/Fgf21 axis via the induction of miR-34a under diet-induced obesity and insulin-resistant conditions.
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