Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany.
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain; Centro de Investigación en Red, Enfermedades Neurodegenerativas (CiberNed), Instituto de Salud Carlos III, Madrid, Spain.
Cell Metab. 2020 Jul 7;32(1):56-70.e7. doi: 10.1016/j.cmet.2020.06.006. Epub 2020 Jun 25.
The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti-obesity potential.
人口老龄化与肥胖症的流行相结合，导致非传染性疾病的惊人上升。在这里，我们表明，神秘的腺苷 A2B 受体 (A2B) 在骨骼肌 (SKM) 以及棕色脂肪组织 (BAT) 中大量表达，可能成为对抗与年龄相关的肌肉萎缩 (肌肉减少症) 和肥胖的靶点。骨骼肌特异性缺失 A2B 的小鼠表现出肌肉减少症、肌肉力量减弱和能量消耗 (EE) 减少，而药理学 A2B 激活则可以对抗这些过程。脂肪组织特异性缺失 A2B 加剧了与年龄相关的过程并减少了 BAT 的 EE，而 A2B 刺激则改善了肥胖。在人类中，A2B 的表达与 SKM、BAT 活性以及白色脂肪中产热脂肪细胞的丰度的 EE 相关。此外，A2B 激动剂治疗可增加人类脂肪细胞、肌细胞和肌肉外植体的 EE。从机制上讲，A2B 形成了腺苷信号所必需的异二聚体。总的来说，腺苷/A2B 信号传递将肌肉和 BAT 联系起来，具有抗衰老和抗肥胖的潜力。
