PPARγ-dependent remodeling of translational machinery in adipose progenitors is impaired in obesity
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.
Authors
- Andrew D. Hildreth (ORCID: https://orcid.org/0000-0001-8447-4817)
- Zaynab Nouhi
- James Akira Wohlschlegel (ORCID: https://orcid.org/0000-0003-3399-901X)
- Mirian Krystel De Siqueira (ORCID: https://orcid.org/0000-0001-9455-7931)
- Timothy E. O’Sullivan (ORCID: https://orcid.org/0000-0003-1435-8188)
- Tamer Sallam (ORCID: https://orcid.org/0000-0001-7144-7393)
- Claudio J. Villanueva (ORCID: https://orcid.org/0000-0002-9731-7463)
- Peter Tontonoz (ORCID: https://orcid.org/0000-0003-1259-0477)
- Shili Xu (ORCID: https://orcid.org/0000-0002-4933-8673)
- Marcus J. Tol
- Gaoyan Li
- Julia J. Mack (ORCID: https://orcid.org/0000-0002-9239-8436)
- Mikayla Tamboline (ORCID: https://orcid.org/0000-0002-3675-2904)
- Xinshu Xiao (ORCID: https://orcid.org/0000-0002-9362-8029)
- Vijaya Pandey (ORCID: https://orcid.org/0000-0002-5675-5504)
- Laura Hulea (ORCID: https://orcid.org/0000-0001-7585-7760)
- Alejandro Schcolnik‐Cabrera (ORCID: https://orcid.org/0000-0001-7734-3253)
- Jakeline Larios (ORCID: https://orcid.org/0000-0001-8526-4408)
- Xia Yang (ORCID: https://orcid.org/0000-0002-3971-038X)
- Siqi Wang (ORCID: https://orcid.org/0000-0002-1491-2962)
- Zhengyi Zhang (ORCID: https://orcid.org/0000-0001-9094-1223)
- Yutian Zhao (ORCID: https://orcid.org/0000-0001-9689-1570)
- In Sook Ahn
Institutions
- University of California, Los Angeles (US)
- Hôpital Maisonneuve-Rosemont (CA)
- Shanghai Institute of Nutrition and Health (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-11-22
- DOI
- https://doi.org/10.1016/j.celrep.2024.114945
- Citations
- 14
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 4.57
Funders
- American Heart Association
- National Institutes of Health
- University of California, Los Angeles
- National Institute of Diabetes and Digestive and Kidney Diseases
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles