Objective

To determine the role of the enterokine, FGF15/19, in adipose tissue thermogenic adaptations.

Methods

Circulating FGF19 and gene expression (qRT-PCR) levels were assessed in subcutaneous adipose tissue from human patients with obesity. Effects of experimentally increased FGF15 and FGF19 levels in vivo were determined in mice using adenoviral and adeno-associated vectors. Adipose tissues were characterized in FGF15-null mice under distinct cold-related thermogenic challenges. The analyses performed spanned metabolic profiling, tissue characterization, histology, gene expression and immunoblot assays.

Results

In humans, FGF19 levels are directly associated with UCP1 gene expression in subcutaneous adipose tissue. Experimental increases of FGF15 or FGF19 induced white fat browning in mice, as evidence by the appearance of multilocular beige cells and markers indicative of a beige phenotype, including increased UCP1 protein levels. Mice lacking FGF15 showed markedly impaired white adipose tissue browning and a mild reduction in parameters indicative of BAT activity in response to cold-induced environmental thermogenic challenges. This was concomitant with signs of altered systemic metabolism, such as reduced glucose tolerance and impaired cold-induced insulin sensitization.

Conclusions

The enterokine FGF15/19 is a key factor required for adipose tissue plasticity in response to thermogenic adaptations.

中文翻译：

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FGF15/19 是响应产热适应的脂肪组织可塑性所必需的

客观的

确定肠因子 FGF15/19 在脂肪组织产热适应中的作用。

方法

在人类肥胖患者的皮下脂肪组织中评估了循环 FGF19 和基因表达 (qRT-PCR) 水平。使用腺病毒和腺相关载体在小鼠中确定实验性增加的 FGF15 和 FGF19 水平在体内的影响。在与寒冷相关的不同产热挑战下，FGF15 缺失小鼠的脂肪组织被表征。进行的分析涵盖代谢谱、组织表征、组织学、基因表达和免疫印迹分析。

结果

在人类中，FGF19 水平与皮下脂肪组织中的 UCP1 基因表达直接相关。FGF15 或 FGF19 的实验增加诱导小鼠白色脂肪褐变，作为证据的证据是多房米色细胞和指示米色表型的标记物的出现，包括增加的 UCP1 蛋白水平。缺乏 FGF15 的小鼠表现出明显受损的白色脂肪组织褐变和指示 BAT 活性的参数轻度降低，以响应寒冷诱导的环境产热挑战。这伴随着全身代谢改变的迹象，例如葡萄糖耐量降低和寒冷诱导的胰岛素敏化受损。

结论

肠因子 FGF15/19 是脂肪组织可塑性响应产热适应所需的关键因素。