小柯机器人

美国德克萨斯大学西南医学中心Rana K. Gupta小组发现，病理性HIF1α信号驱动肥胖中的脂肪前体细胞功能障碍。该研究于2021年2月3日在线发表于国际一流学术期刊《细胞—干细胞》。

研究人员发现，小鼠白色脂肪组织（WAT）PDGFRβ⁺细胞内HIFα诱导的PDGFRβ信号驱动PPARγ（脂肪形成的主要调节因子）的抑制性第112位丝氨酸（S112）磷酸化。WAT PDGFRβ⁺细胞中PPARγ S112磷酸化水平与脂肪储存相关，并且PDGFRβ⁺细胞中PPARγ磷酸化水平与高脂饮食喂养后脂肪形成的能力成反比。PDGFRβ⁺前体细胞中的HIFα抑制作用可促进皮下和腹部内脂肪形成，健康的WAT重塑，并改善肥胖患者的代谢健康状况。

通过用PDGFR拮抗剂Imatinib治疗肥胖小鼠，可以模拟这些代谢益处，后者以前体细胞PPARγ依赖性的方式促进脂肪细胞增生和葡萄糖耐受。这项研究揭示了脂肪前体细胞（APC）对高脂喂养反应的潜在机制，并强调了APC药理靶向改善肥胖代谢健康的潜力。 

据介绍，出于不清楚的原因，APC在对肥胖的反应中表现出区域差异。

附：英文原文

Title: Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity

Author: Mengle Shao, Chelsea Hepler, Qianbin Zhang, Bo Shan, Lavanya Vishvanath, Gervaise H. Henry, Shangang Zhao, Yu A. An, Yibo Wu, Douglas W. Strand, Rana K. Gupta

Issue&Volume: 2021-02-03

Abstract: Adipose precursor cells (APCs) exhibit regional variation in response to obesity,for unclear reasons. Here, we reveal that HIFα-induced PDGFRβ signaling within murinewhite adipose tissue (WAT) PDGFRβ+ cells drives inhibitory serine 112 (S112) phosphorylation of PPARγ, the master regulatorof adipogenesis. Levels of PPARγ S112 phosphorylation in WAT PDGFRβ+ cells are depot dependent, with levels of PPARγ phosphorylation in PDGFRβ+ cells inversely correlating with their capacity for adipogenesis upon high-fat-dietfeeding. HIFα suppression in PDGFRβ+ progenitors promotes subcutaneous and intra-abdominal adipogenesis, healthy WAT remodeling,and improved metabolic health in obesity. These metabolic benefits are mimicked bytreatment of obese mice with the PDGFR antagonist Imatinib, which promotes adipocytehyperplasia and glucose tolerance in a progenitor cell PPARγ-dependent manner. Ourstudies unveil a mechanism underlying depot-specific responses of APCs to high-fatfeeding and highlight the potential for APCs to be targeted pharmacologically to improvemetabolic health in obesity.

DOI: 10.1016/j.stem.2020.12.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30592-0

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