小柯机器人

韩国首尔国立大学Jae Bum Kim小组发现，SREBP1c-PARP1轴调节脂肪细胞的抗衰老活性并改善肥胖症的代谢失衡状况。这一研究成果于2022年4月12日在线发表在国际学术期刊《细胞—代谢》上。

研究人员发现肥胖的脂肪细胞是易衰老的细胞，并伴随着基因组的不稳定性。此外，研究人员发现SREBP1c可能通过调节DNA损伤反应在脂肪细胞的基因组稳定性和衰老中发挥关键作用。出乎意料的是，SREBP1c与PARP1相互作用，并在DNA修复过程中增强PARP1的活性，这与它的典型生脂功能无关。SREBP1c的遗传敲除加速了脂肪细胞的衰老，导致免疫细胞被招募到肥胖的脂肪组织。这些有害的影响引发了肥胖症中不健康的脂肪组织重塑和胰岛素抵抗。相反，消除衰老的脂肪细胞可以减轻脂肪组织的炎症并改善胰岛素抵抗。这些发现揭示了SREBP1c-PARP1轴在调控脂肪细胞衰老中的独特作用，并将有助于破译肥胖症中衰老的代谢意义。

据悉，新的证据表明，衰老细胞的增生与代谢紊乱有关。然而，肥胖症中细胞衰老的潜在机制和代谢后果仍然不明显。

附：英文原文

Title: SREBP1c-PARP1 axis tunes anti-senescence activity of adipocytes and ameliorates metabolic imbalance in obesity

Author: Gung Lee, Ye Young Kim, Hagoon Jang, Ji Seul Han, Hahn Nahmgoong, Yoon Jeong Park, Sang Mun Han, Changyun Cho, Sangsoo Lim, Jung-Ran Noh, Won Keun Oh, Chul-Ho Lee, Sun Kim, Jae Bum Kim

Issue&Volume: 2022-04-12

Abstract: Emerging evidence indicates that the accretion of senescent cells is linked to metabolicdisorders. However, the underlying mechanisms and metabolic consequences of cellularsenescence in obesity remain obscure. In this study, we found that obese adipocytesare senescence-susceptible cells accompanied with genome instability. Additionally,we discovered that SREBP1c may play a key role in genome stability and senescencein adipocytes by modulating DNA-damage responses. Unexpectedly, SREBP1c interactedwith PARP1 and potentiated PARP1 activity during DNA repair, independent of its canonicallipogenic function. The genetic depletion of SREBP1c accelerated adipocyte senescence,leading to immune cell recruitment into obese adipose tissue. These deleterious effectsprovoked unhealthy adipose tissue remodeling and insulin resistance in obesity. Incontrast, the elimination of senescent adipocytes alleviated adipose tissue inflammationand improved insulin resistance. These findings revealed distinctive roles of SREBP1c-PARP1axis in the regulation of adipocyte senescence and will help decipher the metabolicsignificance of senescence in obesity.

DOI: 10.1016/j.cmet.2022.03.010

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00098-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx