Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Am J Physiol Endocrinol Metab. 2021 Feb 1;320(2):E359-E378. doi: 10.1152/ajpendo.00352.2020. Epub 2020 Dec 7.
Cold- and diet-induced recruitment of brown adipose tissue (BAT) and the browning of white adipose tissue (WAT) are dynamic processes, and the recruited state attained is a state of dynamic equilibrium, demanding continuous stimulation to be maintained. An involvement of macrophages, classical proinflammatory (M1) or alternatively activated anti-inflammatory (M2), is presently discussed as being an integral part of these processes. If these macrophages play a mediatory role in the recruitment process, such an involvement would have to be maintained in the recruited state. We have, therefore, investigated whether the recruited state of these tissues is associated with macrophage accretion or attrition. We found no correlation (positive or negative) between total UCP1 mRNA levels (as a measure of recruitment) and proinflammatory macrophages in any adipose depot. We found that in young chow-fed mice, cold-induced recruitment correlated with accretion of anti-inflammatory macrophages; however, such a correlation was not seen when cold-induced recruitment was studied in diet-induced obese mice. Furthermore, the anti-inflammatory macrophage accretion was mediated via β/β-adrenergic receptors; yet, in their absence, and thus in the absence of macrophage accretion, recruitment proceeded normally. We thus conclude that the classical recruited state in BAT and inguinal (brite/beige) WAT is not paralleled by macrophage accretion or attrition. Our results make mediatory roles for macrophages in the recruitment process less likely. A regulatory or mediatory role-positive or negative-for macrophages in the recruitment of brown adipose tissue is presently discussed. As the recruited state in the tissue is a dynamic process, maintenance of the recruited state would need persistent alterations in macrophage complement. Contrary to this expectation, we demonstrate here an absence of alterations in macrophage complement in thermogenically recruited brown-or brite/beige-adipose tissues. Macrophage regulation of thermogenic capacity is thus less likely.
冷刺激和饮食诱导棕色脂肪组织（BAT）的募集以及白色脂肪组织（WAT）的褐变是动态过程，募集所达到的状态是一种动态平衡状态，需要持续刺激来维持。目前认为，巨噬细胞的参与，经典的促炎（M1）或替代性激活的抗炎（M2），是这些过程的一个组成部分。如果这些巨噬细胞在募集过程中发挥中介作用，那么这种参与必须在募集状态下维持。因此，我们研究了这些组织的募集状态是否与巨噬细胞积累或消耗有关。我们发现，在任何脂肪库中，总 UCP1 mRNA 水平（作为募集的衡量标准）与促炎巨噬细胞之间没有相关性（正相关或负相关）。我们发现，在年轻的 Chow 喂养的小鼠中，冷诱导的募集与抗炎巨噬细胞的积累相关；然而，当在饮食诱导肥胖的小鼠中研究冷诱导的募集时，没有观察到这种相关性。此外，抗炎巨噬细胞的积累是通过β/β-肾上腺素能受体介导的；然而，在它们缺失的情况下，即巨噬细胞积累缺失的情况下，募集仍然正常进行。因此，我们得出结论，BAT 和腹股沟（米色/褐色）WAT 的经典募集状态并不伴随着巨噬细胞的积累或消耗。我们的结果使得巨噬细胞在募集过程中的中介作用不太可能。目前正在讨论巨噬细胞在棕色脂肪组织募集中的调节或中介作用（正或负）。由于组织中的募集状态是一个动态过程，募集状态的维持需要持续改变巨噬细胞的补充。与这一预期相反，我们在这里证明，在产热募集的棕色或米色/褐色脂肪组织中，巨噬细胞补充没有改变。因此，巨噬细胞对产热能力的调节不太可能。
