Mfn2 is critical for brown adipose tissue thermogenic function.
Mfn2 is critical for brown adipose tissue thermogenic function.
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DOI：
10.15252/embj.201694914
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发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Cantó C
中科院分区：
文献类型：
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作者：
Boutant M;Kulkarni SS;Joffraud M;Ratajczak J;Valera-Alberni M;Combe R;Zorzano A;Cantó C
线粒体融合和裂变事件，统称为线粒体动力学，作为质量控制机制，以确保线粒体功能和微调细胞生物能量学。骨骼肌中线粒体融合蛋白2（Mfn 2）表达缺陷和线粒体分裂增强是胰岛素抵抗状态的标志。有趣的是，Mfn 2在棕色脂肪组织（BAT）中高度表达，但其作用尚未探索。使用脂肪特异性Mfn 2敲除（Mfn 2-adKO）小鼠，我们证明了BAT中Mfn 2而不是Mfn 1的缺乏会导致严重的BAT功能障碍，与呼吸能力受损和对肾上腺素能刺激的反应迟钝相关。重要的是，Mfn 2直接与周脂蛋白1相互作用，促进线粒体和脂滴之间的相互作用，以响应肾上腺素能刺激。令人惊讶的是，Mfn 2-adKO小鼠免受高脂饮食诱导的胰岛素抵抗和肝脏脂肪变性的影响。总之，这些结果表明Mfn 2是线粒体与脂滴相互作用的介体，影响脂解过程和全身能量稳态。
Mitochondrial fusion and fission events, collectively known as mitochondrial dynamics, act as quality control mechanisms to ensure mitochondrial function and fine‐tune cellular bioenergetics. Defective mitofusin 2 (Mfn2) expression and enhanced mitochondrial fission in skeletal muscle are hallmarks of insulin‐resistant states. Interestingly, Mfn2 is highly expressed in brown adipose tissue (BAT), yet its role remains unexplored. Using adipose‐specific Mfn2 knockout (Mfn2‐adKO) mice, we demonstrate that Mfn2, but not Mfn1, deficiency in BAT leads to a profound BAT dysfunction, associated with impaired respiratory capacity and a blunted response to adrenergic stimuli. Importantly, Mfn2 directly interacts with perilipin 1, facilitating the interaction between the mitochondria and the lipid droplet in response to adrenergic stimulation. Surprisingly, Mfn2‐adKO mice were protected from high‐fat diet‐induced insulin resistance and hepatic steatosis. Altogether, these results demonstrate that Mfn2 is a mediator of mitochondria to lipid droplet interactions, influencing lipolytic processes and whole‐body energy homeostasis.