Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Department of Pharmacology and Regenerative Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Division of Cardiology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Dev Cell. 2021 Apr 5;56(7):985-999.e4. doi: 10.1016/j.devcel.2021.02.018. Epub 2021 Mar 11.
Thermogenic beige fat found in white adipose tissue is a potential therapeutic target to curb the global obesity and diabetes epidemic. However, these inducible thermogenic beige adipocytes have been thought to be short-lived and to rapidly convert to "white-like" adipocytes after discontinuing stimuli. In this study, using effective labeling techniques and genetic mouse tools, we demonstrate that a subset of UCP1+ cells that exist within white adipose tissue are able to self-divide and contribute to new beige adipocyte recruitment in response to β3 stimuli. When these cells are depleted or their adipogenic capability is blocked, β3-induced beige adipocyte formation is impaired. We also identify a cell-cycle machinery of p21 and CDKN2A as a molecular basis of beige adipocyte regulation. Collectively, our findings provide new insights into the cellular and molecular mechanisms of beige adipocyte regulation and potential therapeutic opportunities to induce the beige phenotype and treat metabolic disease.
白色脂肪组织中发现的产热米色脂肪是抑制全球肥胖和糖尿病流行的潜在治疗靶点。然而，这些可诱导的产热米色脂肪细胞被认为寿命短，并且在停止刺激后会迅速转化为“白色样”脂肪细胞。在这项研究中，我们使用有效的标记技术和遗传小鼠工具，证明了在白色脂肪组织中存在的 UCP1+细胞的一个亚群能够自我分裂，并在响应β3 刺激时有助于新的米色脂肪细胞募集。当这些细胞被耗尽或其脂肪生成能力被阻断时，β3 诱导的米色脂肪细胞形成受损。我们还确定了细胞周期机制 p21 和 CDKN2A 作为米色脂肪细胞调节的分子基础。总之，我们的研究结果为米色脂肪细胞调节的细胞和分子机制提供了新的见解，并为诱导米色表型和治疗代谢疾病提供了潜在的治疗机会。
