Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.
Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.
复制标题
DOI：
10.1038/nm.4316
复制
发表时间：
2017-05
期刊：
影响因子：
82.9
通讯作者：
Buettner C
中科院分区：
文献类型：
--
作者：
Fischer K;Ruiz HH;Jhun K;Finan B;Oberlin DJ;van der Heide V;Kalinovich AV;Petrovic N;Wolf Y;Clemmensen C;Shin AC;Divanovic S;Brombacher F;Glasmacher E;Keipert S;Jastroch M;Nagler J;Schramm KW;Medrikova D;Collden G;Woods SC;Herzig S;Homann D;Jung S;Nedergaard J;Cannon B;Tschöp MH;Müller TD;Buettner C
适应性产热是机体对寒冷刺激产生热量的过程，受交感神经系统控制，其主要效应物是儿茶酚胺去甲肾上腺素（NE）。NE通过β3肾上腺素能受体激活棕色脂肪组织以及使白色脂肪组织“褐变”来增强产热。近期研究报道，巨噬细胞在白细胞介素 - 4（IL - 4）刺激下的选择性激活可诱导儿茶酚胺合成途径中的关键酶——酪氨酸羟化酶（TH）的表达，并在产热过程中提供局部产生儿茶酚胺的替代来源。我们在此报道，在成年小鼠的造血细胞中缺失Th既不改变寒冷暴露时的能量消耗，也不减少腹股沟脂肪组织的褐变。骨髓来源的巨噬细胞在受到白细胞介素 - 4（IL - 4）刺激时不会释放NE，并且来自IL - 4刺激的巨噬细胞的条件培养基不能诱导产热基因的表达，例如在用该条件培养基培养的脂肪细胞中解偶联蛋白1（Ucp1）的基因。此外，慢性IL - 4处理不能增加野生型（WT）、Ucp1 - / - 和Il4ra - / - 小鼠的能量消耗。与这些发现一致的是，脂肪组织驻留巨噬细胞不表达TH。因此，我们得出结论，选择性激活的巨噬细胞不会合成大量相关的儿茶酚胺，因此不太可能在脂肪细胞代谢或适应性产热中发挥直接作用。
Adaptive thermogenesis is the process of heat generation in response to cold stimulation and is under the control of the sympathetic nervous system whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through beta3 adrenergic receptors to activate brown adipose tissue and by “browning” white adipose tissue. Recent studies reported that the alternative activation of macrophages in response to IL-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and to provide an alternative source of locally produced catecholamines during the thermogenic process. We here report that the deletion of Th in hematopoetic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with Interleukin-4 (IL-4), and conditioned media from IL-4 stimulated macrophages failed to induce expression of thermogenic genes, such as the one for uncoupling protein 1 (Ucp1) in adipocytes cultured with the conditioned media. Further, chronic IL-4 treatment failed to increase energy expenditure in WT, Ucp1-/- and Il4ra-/- mice. Consistent with these findings, adipose tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines and hence are not likely to play a direct role in adipocyte metabolism or adaptive thermogenesis.