LaPensee Christopher R, Lin Grace, Dent Alexander L, Schwartz Jessica
Department of Molecular & Integrative Physiology, Univ Michigan, Ann Arbor, Michigan, United States of America.
Graduate Program in Cellular & Molecular Biology, Univ Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2014 Jun 3;9(6):e97090. doi: 10.1371/journal.pone.0097090. eCollection 2014.
The transcriptional repressor B-cell Lymphoma 6 (Bcl6) was recently identified in a profile of genes regulated in adipocytes, suggesting a relationship between Bcl6 and metabolic regulation. As a representative target gene repressed by Bcl6, Suppressor of Cytokine Signaling (Socs) 2 expression was elevated in Bcl6 deficient (KO) mice, including metabolic tissues liver, adipose tissue and muscle, as well as in spleen and thymus. Bcl6 occupied the Socs2 promoter in wild-type, but not Bcl6 KO mice, suggesting direct regulation of Socs2 by Bcl6 in vivo. Mice deficient in Bcl6 were found to exhibit multiple features of dysregulated lipid metabolism. Adipose tissue mass was dramatically reduced or absent in Bcl6 KO mice. Further, hepatic and serum triglycerides were low. Bcl6 deficiency was accompanied by decreased hepatic expression of Stearoyl-CoA desaturase 1 (Scd1) and Fatty acid synthase (Fasn) genes which encode lipogenic enzymes. Expression of the gene for the transcription factor Carbohydrate-Responsive Element Binding Protein (Chrebp), which regulates expression of lipogenic genes, was also reduced in liver of Bcl6 KO mice. Bcl6 deficiency disrupted fasting-induced increases in hepatic triglyceride deposition, but not decreases in lipogenic gene expression. Taken together, these findings suggest that in addition to its well-recognized roles in immune regulation, Bcl6 plays a role in regulatory events of lipid metabolism, and that in the absence of Bcl6, lipid metabolism in liver and adipose tissue is dysregulated.
转录抑制因子B细胞淋巴瘤6（Bcl6）最近在脂肪细胞中受调控的基因谱中被鉴定出来，这表明Bcl6与代谢调节之间存在关联。作为被Bcl6抑制的代表性靶基因，细胞因子信号转导抑制因子（Socs）2在Bcl6缺陷（KO）小鼠的多种组织中表达升高，这些组织包括代谢组织肝脏、脂肪组织和肌肉，以及脾脏和胸腺。在野生型小鼠而非Bcl6 KO小鼠中，Bcl6占据了Socs2启动子区域，这表明在体内Bcl6可直接调控Socs2。研究发现，Bcl6缺陷的小鼠表现出脂质代谢失调的多种特征。Bcl6 KO小鼠的脂肪组织量显著减少或缺失。此外，肝脏和血清中的甘油三酯水平较低。Bcl6缺陷伴随着肝脏中硬脂酰辅酶A去饱和酶1（Scd1）和脂肪酸合酶（Fasn）基因表达的降低，这两个基因编码生脂酶。在Bcl6 KO小鼠的肝脏中，调控生脂基因表达的转录因子碳水化合物反应元件结合蛋白（Chrebp）的基因表达也降低。Bcl6缺陷破坏了禁食诱导的肝脏甘油三酯沉积增加，但并未影响生脂基因表达的降低。综上所述，这些发现表明，除了在免疫调节中广为人知的作用外，Bcl6在脂质代谢的调控过程中也发挥作用，并且在缺乏Bcl6的情况下，肝脏和脂肪组织中的脂质代谢会失调。
