De Siqueira Mirian Krystel, Li Gaoyan, Zhao Yutian, Wang Siqi, Ahn In Sook, Tamboline Mikayla, Hildreth Andrew D, Larios Jakeline, Schcolnik-Cabrera Alejandro, Nouhi Zaynab, Zhang Zhengyi, Tol Marcus J, Pandey Vijaya, Xu Shili, O'Sullivan Timothy E, Mack Julia J, Tontonoz Peter, Sallam Tamer, Wohlschlegel James A, Hulea Laura, Xiao Xinshu, Yang Xia, Villanueva Claudio J
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China.
Cell Rep. 2024 Dec 24;43(12):114945. doi: 10.1016/j.celrep.2024.114945. Epub 2024 Nov 22.
Adipose tissue regulates energy homeostasis and metabolic function, but its adaptability is impaired in obesity. In this study, we investigate the impact of acute PPARγ agonist treatment in obese mice and find significant transcriptional remodeling of cells in the stromal vascular fraction (SVF). Using single-cell RNA sequencing, we profile the SVF of inguinal and epididymal adipose tissue of obese mice following rosiglitazone treatment and find an induction of ribosomal factors in both progenitor and preadipocyte populations, while expression of ribosomal factors is reduced with obesity. Notably, the expression of a subset of ribosomal factors is directly regulated by PPARγ. Polysome profiling of the epididymal SVF shows that rosiglitazone promotes translational selectivity of mRNAs that encode pathways involved in adipogenesis and lipid metabolism. Inhibition of translation using a eukaryotic translation initiation factor 4A (eIF4A) inhibitor is sufficient in blocking adipogenesis. Our findings shed light on how PPARγ agonists promote adipose tissue plasticity in obesity.
脂肪组织调节能量平衡和代谢功能，但其适应性在肥胖状态下受损。在本研究中，我们探究了急性过氧化物酶体增殖物激活受体γ（PPARγ）激动剂处理对肥胖小鼠的影响，并发现基质血管部分（SVF）细胞发生了显著的转录重塑。使用单细胞RNA测序技术，我们对罗格列酮处理后的肥胖小鼠腹股沟和附睾脂肪组织的SVF进行了分析，发现祖细胞和前脂肪细胞群体中核糖体因子均有诱导表达，而核糖体因子的表达在肥胖状态下降低。值得注意的是，一部分核糖体因子的表达直接受PPARγ调控。附睾SVF的多聚核糖体分析表明，罗格列酮促进了参与脂肪生成和脂质代谢途径的mRNA的翻译选择性。使用真核翻译起始因子4A（eIF4A）抑制剂抑制翻译足以阻断脂肪生成。我们的研究结果揭示了PPARγ激动剂如何促进肥胖状态下脂肪组织的可塑性。
