Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits

Masand Ruchi; Paulo Esther; Wu Dongmei; Wang Yangmeng; Swaney Danielle L.; Jimenez-Morales David; Krogan Nevan J.; Wang Biao

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Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits

机译：棕色脂肪细胞中线粒体电子传输链的蛋白质组失衡导致代谢益处

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Brown adipose tissue (BAT) thermogenesis is critical for thermoregulation and contributes to total energy expenditure. However, whether BAT has non-thermogenic functions is largely unknown. Here, we describe that BAT-specific liver kinase b1 knockout (Lkb1(BKO)) mice exhibited impaired BAT mitochondrial respiration and thermogenesis but reduced adiposity and liver triglyceride accumulation under high-fat-diet feeding at room temperature. Importantly, these metabolic benefits were also present in Lkb1(BKO) mice at thermoneutrality, where BAT thermogenesis was not required. Mechanistically, decreased mRNA levels of mtDNA-encoded electron transport chain (ETC) subunits and ETC proteome imbalance led to defective BAT mitochondrial respiration in Lkb1(BKO) mice. Furthermore, reducing mtDNA gene expression directly in BAT by removing mitochondrial transcription factor A (Tfam) in BAT also showed ETC proteome imbalance and the trade-off between BAT thermogenesis and systemic metabolism at room temperature and thermoneutrality. Collectively, our data demonstrate that ETC proteome imbalance in BAT regulates systemic metabolism independently of thermogenesis.

机译：棕色脂肪组织（BAT）产热对体温调节至关重要，并有助于总能量消耗。然而，蝙蝠是否具有非产热功能在很大程度上是未知的。在这里，我们描述了蝙蝠特异性肝激酶b1基因敲除（Lkb1（BKO））小鼠在室温下高脂饮食喂养下表现出蝙蝠线粒体呼吸和产热受损，但肥胖和肝脏甘油三酯积累减少。重要的是，这些代谢益处也存在于Lkb1（BKO）小鼠的热中性中，而不需要蝙蝠产热。机制上，线粒体DNA编码的电子传递链（ETC）亚单位的mRNA水平降低和ETC蛋白质组失衡导致Lkb1（BKO）小鼠的蝙蝠线粒体呼吸缺陷。此外，通过去除蝙蝠中的线粒体转录因子A（Tfam）直接降低蝙蝠中的线粒体DNA基因表达，也显示出ETC蛋白质组失衡，以及蝙蝠在室温和热中性条件下产热和系统代谢之间的权衡。总的来说，我们的数据表明BAT中的ETC蛋白质组失衡独立于产热调节系统代谢。

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《Cell metabolism》 |2018年第3期|共18页
作者
Masand Ruchi; Paulo Esther; Wu Dongmei; Wang Yangmeng; Swaney Danielle L.; Jimenez-Morales David; Krogan Nevan J.; Wang Biao;
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Univ Calif San Francisco Cardiovasc Res Inst Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Cardiovasc Res Inst Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Cardiovasc Res Inst Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Cardiovasc Res Inst Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Cellular &

Mol Pharmacol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Cellular &

Mol Pharmacol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Cellular &

Mol Pharmacol San Francisco CA 94158 USA;

Univ Calif San Francisco Cardiovasc Res Inst Dept Physiol San Francisco CA 94158 USA;

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正文语种 eng
中图分类内分泌腺疾病及代谢病;
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Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits

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