Key Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Key Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Clinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Nonglinxi Road 19, Guangzhou, Guangdong, 510080, PR China.
Mol Metab. 2019 Oct;28:48-57. doi: 10.1016/j.molmet.2019.07.004. Epub 2019 Jul 5.
The T-box gene Tbx15 is abundantly expressed in adipose tissues, especially subcutaneous and brown fat. Although its expression is correlated with obesity, its precise biological role in adipose tissue is poorly understood in vivo. Here we investigated the function of Tbx15 in brown adipose thermogenesis and white adipose browning in vivo.
In the present study, we generated adipose-specific Tbx15 knockout (AKO) mice by crossing Tbx15 floxed mice with adiponectin-Cre mice to delineate Tbx15 function in adipose tissues. We systematically investigated the influence of Tbx15 on brown adipose thermogenesis and white adipose browning in mice, as well as the possible underlying molecular mechanism.
Upon cold exposure, adipocyte browning in inguinal adipose tissue was significantly impaired in Tbx15 AKO mice. Furthermore, ablation of Tbx15 blocked adipocyte browning induced by β3 adrenergic agonist CL 316243, which did not appear to alter the expression of Tbx15. Analysis of DNA binding sites using chromatin-immunoprecipitation (ChIP) revealed that TBX15 bound directly to a key region in the Prdm16 promoter, indicating it regulates transcription of Prdm16, the master gene for adipocyte thermogenesis and browning. Compared to control mice, Tbx15 AKO mice displayed increased body weight gain and decreased whole body energy expenditure in response to high fat diets.
Taken together, these findings suggest that Tbx15 regulates adipocyte browning and might be a potential target for the treatment of obesity.
T 盒基因 Tbx15 在脂肪组织中大量表达，特别是在皮下和棕色脂肪中。尽管其表达与肥胖有关，但在体内对其在脂肪组织中的精确生物学作用仍知之甚少。在这里，我们研究了 Tbx15 在棕色脂肪产热和白色脂肪棕色化中的体内功能。
在本研究中，我们通过将 Tbx15 基因 floxed 小鼠与脂联素-Cre 小鼠杂交，生成脂肪组织特异性 Tbx15 敲除（AKO）小鼠，以描绘 Tbx15 在脂肪组织中的功能。我们系统地研究了 Tbx15 对棕色脂肪产热和白色脂肪棕色化的影响，以及可能的潜在分子机制。
在冷暴露下，腹股沟脂肪组织中的脂肪细胞棕色化在 Tbx15 AKO 小鼠中显著受损。此外，Tbx15 的缺失阻止了β3 肾上腺素能激动剂 CL 316243 诱导的脂肪细胞棕色化，而这似乎并没有改变 Tbx15 的表达。使用染色质免疫沉淀（ChIP）分析 DNA 结合位点表明，TBX15 直接结合到 Prdm16 启动子的关键区域，表明它调节 Prdm16 的转录，Prdm16 是脂肪细胞产热和棕色化的主基因。与对照小鼠相比，Tbx15 AKO 小鼠在高脂肪饮食下表现出体重增加和全身能量消耗减少。
综上所述，这些发现表明 Tbx15 调节脂肪细胞棕色化，可能是肥胖治疗的潜在靶点。
