FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue.
FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue.
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DOI：
10.1016/j.molmet.2017.03.009
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发表时间：
2017-06
影响因子：
8.1
通讯作者：
Potthoff MJ
中科院分区：
文献类型：
--
作者：
Markan KR;Naber MC;Small SM;Peltekian L;Kessler RL;Potthoff MJ
成纤维细胞生长因子21 （FGF21）是一种调节代谢稳态的内分泌激素。先前的研究表明，脂肪组织中FGF21信号的损伤可能是通过FGF21专性共受体β-klotho的下调而发生的，而β-klotho会在饮食诱导的肥胖发病期间导致“FGF21抵抗”。在这里，我们试图确定脂肪组织中β-klotho表达的维持是否会阻止FGF21的抵抗，以及其他机制是否也有助于体内FGF21的抵抗。我们培育了脂肪特异性β-klotho转基因小鼠，以确定维持脂肪组织中β-klotho的表达是否能阻止体内FGF21的抗性。在饮食性肥胖期间，白色脂肪组织中β-klotho蛋白水平显著降低，但肝脏或棕色脂肪组织中没有。维持脂肪组织中β-klotho蛋白的表达不会减轻白色脂肪中受损的FGF21信号，也不会增加体内FGF21的敏感性。在白色脂肪组织中，β-klotho表达下调并不是导致白色脂肪组织中FGF21信号受损的主要机制。
Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates metabolic homeostasis. Previous work has suggested that impairment of FGF21 signaling in adipose tissue may occur through downregulation of the obligate FGF21 co-receptor, β-klotho, which leads to “FGF21 resistance” during the onset of diet-induced obesity. Here, we sought to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance and whether other mechanisms also contribute to FGF21 resistance in vivo. We generated adipose-specific β-klotho transgenic mice to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance in vivo. β-klotho protein levels are markedly decreased in white adipose tissue, but not liver or brown adipose tissue, during diet-induced obesity. Maintenance of β-klotho protein expression in adipose tissue does not alleviate impaired FGF21 signaling in white adipose or increase FGF21 sensitivity in vivo. In white adipose tissue, downregulation of β-klotho expression is not the major mechanism contributing to impaired FGF21 signaling in white adipose tissue.