Beige Adipocyte Maintenance Is Regulated by Autophagy-Induced Mitochondrial Clearance.
Beige Adipocyte Maintenance Is Regulated by Autophagy-Induced Mitochondrial Clearance.
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DOI：
10.1016/j.cmet.2016.08.002
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发表时间：
2016-09-13
期刊：
影响因子：
29
通讯作者：
Kajimura S
中科院分区：
文献类型：
--
作者：
Altshuler-Keylin S;Shinoda K;Hasegawa Y;Ikeda K;Hong H;Kang Q;Yang Y;Perera RM;Debnath J;Kajimura S
米色脂肪细胞作为一种替代的细胞靶点在减肥治疗中得到了广泛的关注。虽然最近的研究已经确定了一些促进米色脂肪细胞分化的调节电路，但米色脂肪细胞维持的分子基础仍然不清楚。在这里，我们证明米色脂肪细胞在退出外界刺激后逐渐失去其形态和分子特征，并绕过中间前体阶段直接获得白色样特征。脂肪细胞从米色到白色的转变与线粒体减少、自噬增加以及激活MIT/TFE转录因子介导的溶酶体生物发生密切相关。自噬途径对线粒体在转变过程中的清除至关重要；通过UCP1+-脂肪细胞特异性缺失ATG5或ATG12来抑制自噬，可以防止米色脂肪细胞在退出外部刺激后丢失，保持高发热能力，并防止饮食诱导的肥胖和胰岛素抵抗。本研究揭示了自噬介导的线粒体清除控制米色脂肪细胞维持的基本机制，从而为对抗肥胖提供了新的机会。当暴露于热刺激时，米色脂肪细胞瞬时表达UCP1，但当刺激取消时，该表达消失。XXX等人研究了米色脂肪细胞的维持，并表明自噬介导的线粒体清除是米色脂肪细胞向白色脂肪细胞逆转所必需的。抑制自噬即使在刺激撤除后仍能维持功能上的米色脂肪细胞。
Beige adipocytes gained much attention as an alternative cellular target in anti-obesity therapy. While recent studies have identified a number of regulatory circuits that promote beige adipocyte differentiation, the molecular basis of beige adipocyte maintenance remains unknown. Here, we demonstrate that beige adipocytes progressively lose their morphological and molecular characteristics after withdrawing external stimuli, and directly acquire white-like characteristics bypassing an intermediate precursor stage. The beige-to-white adipocyte transition is tightly coupled to a decrease in mitochondria, increase in autophagy, and activation of MiT/TFE transcription factor-mediated lysosome biogenesis. The autophagy pathway is crucial for mitochondrial clearance during the transition; inhibiting autophagy by UCP1+-adipocyte-specific deletion of Atg5 or Atg12 prevents beige adipocyte loss after withdrawing external stimuli, maintenaning high thermogenic capacity and protecting against diet-induced obesity and insulin resistance. The present study uncovers a fundamental mechanism by which autophagy-mediated mitochondrial clearance controls beige adipocyte maintenance, thereby providing new opportunities to counteract obesity. When exposed to thermogenic stimuli, beige adipocytes transiently express UCP1 but lose that expression upon stimuli withdrawal. XXX et al investigate beige adipocyte maintenance and show that autophagy-mediated mitochondrial clearance is needed for beige to white adipocyte reversal. Inhibition of autophagy maintains functional beige adipocytes even after stimuli withdrawal.
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影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
影响因子：
64.8
作者：
Lee, Jae Man;Wagner, Martin;Xiao, Rui;Kim, Kang Ho;Feng, Dan;Lazar, Mitchell A.;Moore, David D.
通讯作者：
Moore, David D.
Atg7 调节 p53 活性以调节代谢应激期间的细胞周期和存活
DOI：
10.1126/science.1218395
发表时间：
2012-04-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lee IH;Kawai Y;Fergusson MM;Rovira II;Bishop AJ;Motoyama N;Cao L;Finkel T
通讯作者：
Finkel T
影响因子：
10.5
作者：
Kajimura, Shingo;Seale, Patrick;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.