연구논문

세부과제번호 2013M3A9D5072550 단계 1단계 3차년도
세부과제명 마우스 운동 및 대사표현형 분석 기반 구축 및 서비스 제공 공동 유/무 N
SCI여부 Y 게재년월 2016-07
논문제목 The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling.
총저자명 H-J KwonS-N KimY-A KimY-H Lee
학술지명 Cell Death Dis 게재권(호) 7(6)
저널구분 - 페이지수 2285
참여연구원 이윤희 연구책임자 성제경
과제기여도 30 PMID 27362803
사사기관수 - IF (년도) 5.014
제1저자 권현정 교신저자 이윤희
공동저자 -
초록
Cellular plasticity in adipose tissue involves adipocyte death, its clearance, and de novo adipogenesis, enabling homeostatic turnover and adaptation to metabolic challenges; however, mechanisms regulating these serial events are not fully understood. The present study investigated the roles of arachidonate 15-lipoxygenase (Alox15) in the clearance of dying adipocytes by adipose tissue macrophages. First, upregulation of Alox15 expression and apoptotic adipocyte death in gonadal white adipose tissue (gWAT) were characterized during adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Next, an in vitro reconstruction of adipose tissue macrophages and apoptotic adipocytes recapitulated adipocyte clearance by macrophages and demonstrated that macrophages co-cultured with apoptotic adipocytes increased the expression of efferocytosis-related genes. Genetic deletion and pharmacological inhibition of Alox15 diminished the levels of adipocyte clearance by macrophages in a co-culture system. Gene expression profiling of macrophages isolated from gWAT of Alox15 knockout (KO) mice demonstrated distinct phenotypes, especially downregulation of genes involved in lipid uptake and metabolism compared to wild-type mice. Finally, in vivo β3-adrenergic stimulation in Alox15 KO mice failed to recruit crown-like structures, a macrophage network clearing dying adipocytes in gWAT. Consequently, in Alox15 KO mice, proliferation/differentiation of adipocyte progenitors and β3-adrenergic remodeling of gWAT were impaired compared to wild-type control mice. Collectively, our data established a pivotal role of Alox15 in the resolution of adipocyte death and in adipose tissue remodeling.
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