The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes.
The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes.
复制标题
DOI：
10.1016/j.jlr.2021.100102
复制
发表时间：
2021
影响因子：
6.5
通讯作者：
Mueller E
中科院分区：
文献类型：
--
作者：
Perie L;Verma N;Mueller E
叉头盒转录因子已被证明参与各种发育和分化过程。特别是，FoxP 家族成员先前已因其参与肺和神经元细胞分化以及 T 细胞发育和功能的调节而被深入表征；然而，它们在脂肪细胞功能中的作用尚未得到研究。在这里，我们首次报告叉头盒 P4 (FoxP4) 在皮下脂肪库和成熟产热脂肪细胞中高水平表达。通过分子和基因表达分析，我们揭示了 FoxP4 在体内和分离的细胞中响应生热刺激而被诱导，并通过 FoxP4 近端启动子区域中鉴定的热休克反应元件直接受到热休克因子蛋白 1 的调节。涉及染色质免疫沉淀和荧光素酶测定的进一步详细分析表明，FoxP4 直接控制解偶联蛋白 1 的水平，解偶联蛋白 1 是生热作用的关键调节因子，可将脂肪酸氧化与 ATP 生成解偶联。此外，通过我们的功能获得和功能丧失研究，我们发现 FoxP4 调节许多经典棕色和米色脂肪基因的表达，并影响分离脂肪细胞的耗氧量。总的来说，我们的数据首次证明了 FoxP4 在生热脂肪细胞功能调节中的新作用。
Forkhead box transcription factors have been shown to be involved in various developmental and differentiation processes. In particular, members of the FoxP family have been previously characterized in depth for their participation in the regulation of lung and neuronal cell differentiation and T-cell development and function; however, their role in adipocyte functionality has not yet been investigated. Here, we report for the first time that Forkhead box P4 (FoxP4) is expressed at high levels in subcutaneous fat depots and mature thermogenic adipocytes. Through molecular and gene expression analyses, we revealed that FoxP4 is induced in response to thermogenic stimuli, both in vivo and in isolated cells, and is regulated directly by the heat shock factor protein 1 through a heat shock response element identified in the proximal promoter region of FoxP4. Further detailed analysis involving chromatin immunoprecipitation and luciferase assays demonstrated that FoxP4 directly controls the levels of uncoupling protein 1, a key regulator of thermogenesis that uncouples fatty acid oxidation from ATP production. In addition, through our gain-of-function and loss-of-function studies, we showed that FoxP4 regulates the expression of a number of classic brown and beige fat genes and affects oxygen consumption in isolated adipocytes. Overall, our data demonstrate for the first time the novel role of FoxP4 in the regulation of thermogenic adipocyte functionality.
登录
查看更多内容
DOI：
10.1002/wdev.375
发表时间：
2020-09
期刊：
Wiley interdisciplinary reviews. Developmental biology
影响因子：
--
作者：
Co M;Anderson AG;Konopka G
通讯作者：
Konopka G
影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
影响因子：
4.1
作者：
Perie, Luce;Verma, Narendra;Mueller, Elisabetta
通讯作者：
Mueller, Elisabetta
影响因子：
16.6
作者：
Abe, Yohei;Rozqie, Royhan;Matsumura, Yoshihiro;Kawamura, Takeshi;Nakaki, Ryo;Tsurutani, Yuya;Tanimura-Inagaki, Kyoko;Shiono, Akira;Magoori, Kenta;Nakamura, Kanako;Ogi, Shotaro;Kajimura, Shingo;Kimura, Hiroshi;Tanaka, Toshiya;Fukami, Kiyoko;Osborne, Timothy F.;Kodama, Tatsuhiko;Aburatani, Hiroyuki;Inagaki, Takeshi;Sakai, Juro
通讯作者：
Sakai, Juro
影响因子：
29
作者：
Ma, Xinran;Xu, Lingyan;Mueller, Elisabetta
通讯作者：
Mueller, Elisabetta