Mössenböck Karin, Vegiopoulos Alexandros, Rose Adam J, Sijmonsma Tjeerd P, Herzig Stephan, Schafmeier Tobias
Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany.
Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany; Junior research group Metabolism and Stem Cell Plasticity, German Cancer Research Center (DKFZ), Heidelberg, Germany.
PLoS One. 2014 Oct 14;9(10):e110428. doi: 10.1371/journal.pone.0110428. eCollection 2014.
Presence of thermogenically active adipose tissue in adult humans has been inversely associated with obesity and type 2 diabetes. While it had been shown that insulin is crucial for the development of classical brown fat, its role in development and function of inducible brown-in-white (brite) adipose tissue is less clear. Here we show that insulin deficiency impaired differentiation of brite adipocytes. However, adrenergic stimulation almost fully induced the thermogenic program under these settings. Although brite differentiation of adipocytes as well as browning of white adipose tissue entailed substantially elevated glucose uptake by adipose tissue, the capacity of insulin to stimulate glucose uptake surprisingly was not higher in the brite state. Notably, in line with the insulin-independent stimulation of glucose uptake, our data revealed that brite recruitment results in induction of solute carrier family 2 (GLUT-1) expression in adipocytes and inguinal WAT. These results for the first time demonstrate that insulin signaling is neither essential for brite recruitment, nor is it improved in cells or tissues upon browning.
在成年人体内，具有产热活性的脂肪组织的存在与肥胖和2型糖尿病呈负相关。虽然已经表明胰岛素对经典棕色脂肪的发育至关重要，但其在诱导性米色脂肪组织（brite）的发育和功能中的作用尚不清楚。在这里，我们表明胰岛素缺乏会损害brite脂肪细胞的分化。然而，在这些情况下，肾上腺素能刺激几乎完全诱导了产热程序。虽然脂肪细胞的brite分化以及白色脂肪组织的褐变需要脂肪组织显著提高葡萄糖摄取，但令人惊讶的是，胰岛素刺激葡萄糖摄取的能力在brite状态下并不更高。值得注意的是，与葡萄糖摄取的胰岛素非依赖性刺激一致，我们的数据显示brite募集导致脂肪细胞和腹股沟白色脂肪组织中溶质载体家族2（GLUT-1）表达的诱导。这些结果首次证明胰岛素信号传导对于brite募集既不是必需的，在褐变后的细胞或组织中也没有改善。
