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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.1
- 수록면
- 603 - 614 (12page)
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Higher levels of body fat are associated with an increased risk for development numerous adverse health conditions. FTY720 is an immune modulator and a synthetic analogue of sphingosine 1-phosphate (S1P), activated S1P receptors and is effective in experimental models of transplantation and autoimmunity. Whereas immune modulation by FTY720has been extensively studied, other actions of FTY720 are not well understood. Here we describe a novel role of FTY720 in the prevention of obesity, involving the regulation of adipogenesis and lipolysis in vivo and in vitro. Male C57B/6J mice were fed a standard diet or a high fat diet (HFD) without or with FTY720 (0.04 mg/kg, twice a week) for 6 weeks. The HFD induced an accumulation of large adipocytes, down-regulation of phosphorylated AMP-activated protein kinase α (p-AMPKα) and Akt (p-Akt); down-regulation of hormone- sensitive lipase (HSL), adipose triglyceride lipase (ATGL) and perilipin mRNA as well as up-regulation of phosphorylated HSL (p-HSL, Ser563) and glycogen synthase kinase 3 α/β (p-GSK3α/β). All these effects were blunted by FTY720 treatment, which inhibited adipogenesis and promoted lipolysis. Also, FTY720 significantly decreased lipid accumulation in maturing preadipocytes. FTY720 down-regulated the transcriptional levels of the PPARγ, C/EBPα and adiponectin, which are markers of adipogenic differentiation. FTY720 significantly increased the release of glycerol and the expression of the HSL, ATGL and perilipin, which are regulators of lipolysis. These results show that FTY720 prevented obesity by modulating adipogenesis and lipolysis, and suggest that FTY720 is used for the treatment of obesity.
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참고문헌 (23)
참고문헌 신청
Anthonsen MW / 1998 / Identification of Novel Phosphorylation Sites in Hormone-sensitive Lipase That Are Phosphorylated in Response to Isoproterenol and Govern Activation Pro
Arner P / 2005 / Human fat cell lipolysis: biochemistry, regulation and clinical role / Best Pract Res Clin Endocrinol Metab 19 : 471 ~ 482
Bezaire V / 2009 / Chronic TNFα and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis / FEBS lett 583 : 3045 ~
Brinkmann V / 2004 / FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function / Am J Transplant 4 : 1019 ~ 1025
Chiba K / 2005 / FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphat
Arner P / 2005 / Human fat cell lipolysis: biochemistry, regulation and clinical role / Best Pract Res Clin Endocrinol Metab 19 : 471 ~ 482
Bezaire V / 2009 / Chronic TNFα and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis / FEBS lett 583 : 3045 ~
Brinkmann V / 2004 / FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function / Am J Transplant 4 : 1019 ~ 1025
Chiba K / 2005 / FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphat
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