Mitochondrial fatty acid oxidation (FAO) contributes to the proton motive force that drives ATP synthesis in many mammalian tissues. In eutherian (placental) mammals, brown adipose tissue (BAT) can also dissipate this proton gradient through uncoupling protein 1 (UCP1) to generate heat, but the evolutionary events underlying the emergence of BAT are unknown. An essential step in FAO is the transport of cytoplasmic long chain acyl-coenzyme A (acyl-CoA) into the mitochondrial matrix, which requires the action of carnitine palmitoyltransferase 1B (CPT1B) in striated muscle and BAT. In eutherians, the CPT1B gene is closely linked to the choline kinase beta (CHKB) gene, which is transcribed from the same DNA strand and terminates just upstream of CPT1B. CHKB is a rate-limiting enzyme in the synthesis of phosphatidylcholine (PC), a predominant mitochondrial membrane phospholipid, suggesting that the coordinated expression of CHKB and CPT1B may cooperatively enhance mitochondrial FAO. The present findings show that transcription of the eutherian CHKB and CPT1B genes is linked within a unitary epigenetic domain targeted to the CHKB gene, and that that this regulatory linkage appears to have resulted from an intergenic deletion in eutherians that significantly altered the distribution of CHKB and CPT1B expression. Informed by the timing of this event relative to the emergence of BAT, the phylogeny of CHKB-CPT1B synteny, and the insufficiency of UCP1 to account for eutherian BAT, these data support a mechanism for the emergence of BAT based on the acquisition of a novel capacity for adipocyte FAO in a background of extant UCP1.

线粒体脂肪酸氧化 (FAO) 有助于在许多哺乳动物组织中驱动 ATP 合成的质子动力。在eutherian（胎盘）哺乳动物中，棕色脂肪组织（BAT）也可以通过解偶联蛋白1（UCP1）来消散这种质子梯度以产生热量，但BAT出现的进化事件尚不清楚。FAO 的一个重要步骤是将细胞质长链酰基辅酶 A (acyl-CoA) 转运到线粒体基质中，这需要横纹肌和 BAT 中肉碱棕榈酰转移酶 1B (CPT1B) 的作用。在真人动物中，CPT1B基因与胆碱激酶 β ( CHKB ) 基因密切相关，后者从同一条 DNA 链转录并终止于CPT1B。CHKB 是磷脂酰胆碱 (PC) 合成的限速酶，这是一种主要的线粒体膜磷脂，表明CHKB和CPT1B的协同表达可能协同增强线粒体 FAO。目前的研究结果表明，eutherian CHKB和CPT1B基因的转录与针对 CHKB基因的单一表观遗传域有关，并且这种调节联系似乎是由eutherian 中的基因间缺失引起的，该缺失显着改变了CHKB和CPT1B表达。受此事件相对于 BAT 出现的时间、CHKB-CPT1B 同线性的系统发育以及 UCP1 不足以解释eutherian BAT 的影响，这些数据支持了基于获取新的 BAT 出现的 BAT 机制在现存 UCP1 的背景下脂肪细胞粮农组织的能力。