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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제19권 제5호
- 발행연도
- 2015.9
- 수록면
- 451 - 460 (10page)
이용수
초록· 키워드
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Sirtuin 1 (SIRT1) is a mammalian NAD＋ -dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-κB), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.
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참고문헌 (38)
참고문헌 신청
Li X. / 2013 / SIRT1 and energy metabolism / Acta Biochim Biophys Sin(Shanghai) 45:51~60
Smith JS / 2000 / A phylogenetically conserved NAD＋-dependent protein deacetylase activity in the Sir2 protein family / Proc Natl Acad Sci U S A 97:6658~6663
Houtkooper RH / 2012 / Sirtuins as regulators of metabolism and healthspan / Nat Rev Mol Cell Biol 13:225~238
Schug TT / 2010 / Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress / Mol Cell Biol 30:4712~4721
Yeung F / 2004 / Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase / EMBO J 23:2369~2380
Smith JS / 2000 / A phylogenetically conserved NAD＋-dependent protein deacetylase activity in the Sir2 protein family / Proc Natl Acad Sci U S A 97:6658~6663
Houtkooper RH / 2012 / Sirtuins as regulators of metabolism and healthspan / Nat Rev Mol Cell Biol 13:225~238
Schug TT / 2010 / Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress / Mol Cell Biol 30:4712~4721
Yeung F / 2004 / Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase / EMBO J 23:2369~2380
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