Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans.
Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans.
复制标题
可溶性 LR11/SorLA 抑制脂肪组织中的生热作用，并与人类的 BMI 相关。
DOI：
10.1038/ncomms9951
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发表时间：
2015-11-20
影响因子：
16.6
通讯作者：
Bujo H
中科院分区：
文献类型：
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作者：
Whittle AJ;Jiang M;Peirce V;Relat J;Virtue S;Ebinuma H;Fukamachi I;Yamaguchi T;Takahashi M;Murano T;Tatsuno I;Takeuchi M;Nakaseko C;Jin W;Jin Z;Campbell M;Schneider WJ;Vidal-Puig A;Bujo H
棕色脂肪组织（BAT）的产热是哺乳动物能量消耗的重要组成部分。最近的研究证实了它在人体中的存在和代谢作用。因此，明确BAT的生理调控对于制定治疗代谢性疾病的策略具有重要意义。在这里，我们发现低密度脂蛋白受体的可溶性形式，LR11/SorLA (sLR11)，以细胞自主的方式抑制脂肪组织中的产热作用。缺乏LR11的小鼠可以避免与白色脂肪组织褐变增加和高代谢相关的饮食性肥胖。用sLR11处理脂肪细胞可通过骨形态发生蛋白/TGFβ信号通路抑制产热，并降低Smad磷酸化。此外，人类体内的sLR11水平被证明与体重指数和肥胖呈正相关。鉴于需要严格调节具有高能量浪费能力的组织，我们提出LR11在肥胖状态下发挥了被夸大的能量保存作用。棕色脂肪组织（BAT）产热是哺乳动物机体能量消耗的重要决定因素。在这里，Whittle等人报道了蛋白质sLR11是小鼠BAT活性的负调节因子，通过抑制棕色脂肪细胞中的BMP/Smad信号来抑制产热。
Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFβ signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity. Brown adipose tissue (BAT) thermogenesis is an important determinant of organismal energy expenditure in mammals. Here, Whittle et al. report that the protein sLR11 is a negative regulator of BAT activity in mice, repressing thermogenesis by inhibiting BMP/Smad signalling in brown adipocytes.