Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Jan;1864(1):51-58. doi: 10.1016/j.bbalip.2018.06.013. Epub 2018 Jun 14.
In mice living under normal animal house conditions, the brown adipocytes in classical brown adipose tissue depots are already essentially fully differentiated: UCP1 mRNA and UCP1 protein levels are practically saturated. This means that any further recruitment - in response to cold exposure or any other browning agent - does not result in significant augmentation of these parameters. This may easily be construed to indicate that classical brown adipose tissue cannot be further recruited. However, this is far from the case: the capacity for further recruitment instead lies in the ability of the tissue to increase the number of brown-fat cells, a remarkable and highly controlled physiological recruitment process. We have compiled here the available data concerning the unique ability of norepinephrine to increase cell proliferation and inhibit apoptosis in brown adipocytes. Adrenergically stimulated cell proliferation is fully mediated via β-adrenoceptors and occurs through activation of stem cells in the tissue; intracellular mediation of the signal involves cAMP and protein kinase A activation, but activation of Erk1/2 is not part of the pathway. Apoptosis inhibition in brown adipocytes is induced by both β- and α-adrenergic receptors and here the intracellular pathway includes Erk1/2 activation. This unique ability of norepinephrine to increase cell number in an apparently mitogenically dormant tissue provides possibilities to augment the metabolic capacity of brown adipose tissue, also for therapeutic purposes.
在生活在正常动物房条件下的小鼠中，经典棕色脂肪组织储存器中的棕色脂肪细胞已经基本完全分化：UCP1 mRNA 和 UCP1 蛋白水平实际上已达到饱和。这意味着任何进一步的募集——无论是对寒冷暴露还是任何其他褐变剂的反应——都不会导致这些参数的显著增加。这很容易被解释为表明经典棕色脂肪组织不能进一步募集。然而，事实远非如此：进一步募集的能力在于组织增加棕色脂肪细胞数量的能力，这是一个显著的、高度受控的生理募集过程。我们在这里汇编了有关去甲肾上腺素独特能力的可用数据，即增加棕色脂肪细胞增殖并抑制细胞凋亡。肾上腺素能刺激的细胞增殖完全通过β-肾上腺素受体介导，并通过组织中的干细胞激活发生；信号的细胞内中介涉及 cAMP 和蛋白激酶 A 激活，但 Erk1/2 的激活不是该途径的一部分。棕色脂肪细胞中的细胞凋亡抑制是由β-和α-肾上腺素受体诱导的，这里的细胞内途径包括 Erk1/2 激活。去甲肾上腺素增加在明显有丝分裂休眠组织中细胞数量的这种独特能力为增加棕色脂肪组织的代谢能力提供了可能性，也为治疗目的提供了可能性。
