Time: 11:00-12:00 on Thur.,Aug.10, 2023

Zoom：577 327 3402

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Speaker: Dr.Ming Xu

Host: Dr.Xinyu Zhao

Title: Targeting p21Cip1-Highly-Expressing Cells in Adipose Tissue Alleviates Insulin Resistance in Obesity

Abstract：

Insulin resistance is a pathological state often associated with obesity, representing a major risk factor for type 2 diabetes. Limited mechanism-based strategies exist to alleviate insulin resistance. Here, using single-cell transcriptomics, we identify a small, critically important, but previously unexamined cell population, p21Cip1-highly-expressing (p21high) cells, which accumulate in adipose tissue with obesity. By leveraging a p21-Cre mouse model, we demonstrate that intermittent clearance of p21high cells can both prevent and alleviate insulin resistance in obese mice. Exclusive inactivation of the NF-κB pathway within p21high cells, without killing them, attenuates insulin resistance. Moreover, fat transplantation experiments establish that p21high cells within fat are sufficient to cause insulin resistance in vivo. Importantly, a senolytic cocktail, dasatinib plus quercetin, eliminates p21high cells in human fat ex vivo, and mitigates insulin resistance following xenotransplantation into immuno-deficient mice. Our findings lay the foundation for pursuing the targeting of p21high cells as a new therapy to alleviate insulin resistance.

Biography：

Ming Xu received his bachelor degree of Biological Science from Fudan University. He then came to the University of Kansas Medical Center (KUMC) for his graduate studies in 2006. As a graduate student, he mainly worked on the role of Ncb5or on metabolic dysfunction using both animal and cell models. In 2011, he joined Dr. James Kirkland’s lab within Robert and Arlene Kogod Center on Aging at the Mayo Clinic for postdoctoral training. Since then, he have been working extensively on the role of cellular senescence in various age-related diseases including physical dysfunction and metabolic dysfunction, with an emphasis on approaches with translational potential. In 2018, Ming Xu joined the UConn Center on Aging as a tenure-track faculty member. His lab continues to employ novel animal models and human cell transplantation to study the underlying mechanisms by which senescent cells induce tissue dysfunction. In the past four years, Ming Xu has published seven papers as senior corresponding author on impactful journals including Cell Metabolism, Nature Aging (x2), Aging Cell (x2) and npj Regenerative Medicine.