Li Yongguo, Bolze Florian, Fromme Tobias, Klingenspor Martin
Molecular Nutritional Medicine, Technische Universität München, Else Kröner-Fresenius Center, Freising, Germany.
Molecular Nutritional Medicine, Technische Universität München, Else Kröner-Fresenius Center, Freising, Germany.
Biochim Biophys Acta. 2014 Sep;1841(9):1345-52. doi: 10.1016/j.bbalip.2014.06.003. Epub 2014 Jun 19.
BRITE (brown-in-white) cells are brown adipocyte-like cells found in white adipose tissue (WAT) of rodents and/or humans. The recruitment of BRITE adipocytes, referred to as the browning of WAT, is hallmarked by the expression of UCP1 and exerts beneficial metabolic effects. Here we address whether beyond systemic cues depot- and strain-specific variation in BRITE recruitment is determined by a cellular program intrinsic to progenitors. Therefore we compared the browning capacity of serum and investigated brown and BRITE adipogenesis in primary cultures of stromal-vascular cells isolated from interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) in two inbred mouse strains C57BL/6J (B6, a strain with low browning propensity) and 129/S6SvEv (129, a strain with high browning propensity). Paradoxically, serum collected from B6 mice was more potent in the promotion of browning than serum collected from 129 mice. Nevertheless, we demonstrate that depot- and strain-specific differences observed in vivo are pheno-copied in primary cultures in vitro, as judged by UCP1 expression and by functional analysis. Notably, primary adipocytes from 129 mice had a higher capacity for isoproterenol-induced uncoupled respiration than B6. We conclude that cues intrinsic to the progenitor cells contribute to differential BRITE adipogenesis. Further analyses demonstrate that these cues are independent of autocrine/paracrine mechanisms, BRITE progenitor abundance and genetic variation in the gene regulatory region of Ucp1 but rather depend on trans-acting factors. These results provide new insights on the molecular basis of strain and depot-specific differences in BRITE adipogenesis.
BRITE（白中褐）细胞是在啮齿动物和/或人类的白色脂肪组织（WAT）中发现的褐色脂肪细胞样细胞。BRITE脂肪细胞的募集，即WAT的褐变，其特征是UCP1的表达，并发挥有益的代谢作用。在这里，我们探讨除了全身信号外，BRITE募集的特定储存库和品系差异是否由祖细胞固有的细胞程序决定。因此，我们比较了血清的褐变能力，并研究了从肩胛间褐色脂肪组织（iBAT）、腹股沟白色脂肪组织（iWAT）和附睾白色脂肪组织（eWAT）分离的基质血管细胞原代培养物中的褐色和BRITE脂肪生成，这两种细胞来自两个近交小鼠品系C57BL/6J（B6，一种褐变倾向低的品系）和129/S6SvEv（129，一种褐变倾向高的品系）。矛盾的是，从B6小鼠收集的血清比从129小鼠收集的血清更能促进褐变。然而，我们证明，通过UCP1表达和功能分析判断，体内观察到的特定储存库和品系差异在体外原代培养物中表现为表型复制。值得注意的是，129小鼠的原代脂肪细胞比B6小鼠的异丙肾上腺素诱导的解偶联呼吸能力更高。我们得出结论，祖细胞固有的信号有助于BRITE脂肪生成的差异。进一步分析表明，这些信号独立于自分泌/旁分泌机制、BRITE祖细胞丰度和Ucp1基因调控区域的遗传变异，而是依赖于反式作用因子。这些结果为BRITE脂肪生成中品系和储存库特异性差异的分子基础提供了新的见解。
