Single-cell view and a novel protective macrophage subset in perivascular adipose tissue in T2DM.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Vasculopathy underlies diabetic complications, with perivascular adipose tissue (PVAT) playing crucial roles in its development. However, the changes in the cellular composition and function of PVAT, including the specific cell subsets and mechanisms implicated in type 2 diabetes mellitus (T2DM) vasculopathy, remain unclear. Methods To address the above issues, we performed single-cell RNA sequencing on the stromal vascular fraction (SVF) of PVAT from normal and T2DM rats. Then, various bioinformatics tools and functional experiments were used to investigate the characteristic changes in the cellular profile of diabetic PVAT SVF, their implications, and the underlying mechanisms. Results Our study reveals the single-cell landscape of the SVF of PVAT, demonstrating its considerable heterogeneity and significant alterations in T2DM, including an enhanced inflammatory response and elevated proportions of macrophages and natural killer (NK) cells. Moreover, macrophages are critical hubs for cross-talk among various cell populations. Notably, we identified a decreased Pdpn + macrophage subpopulation in the PVAT of T2DM rats and confirmed this in mice and humans. In vitro and in vivo studies demonstrated that Pdpn + macrophages alleviated insulin resistance and modulated adipokine/cytokine expression in adipocytes via the Pla2g2d-DHA/EPA-GPR120 pathway. This subset also en

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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