FGF21 alleviates adipose stem cell senescence via CD90 glycosylation-dependent glucose influx in remodeling healthy white adipose tissue.

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)

The senescence of adipose stem cells (ASCs) impairs healthy adipose tissue remodeling, causing metabolic maladaptation to energy surplus. The intrinsic molecular pathways and potential therapy targets for ASC senescence are largely unclear. Here, we showed that visceral ASCs were prone to senescence that was caused by reactive oxygen species (ROS) overload, especially mitochondrial ROS. These senescent ASCs failed to sustain efficient glucose influx, pentose phosphate pathway (PPP) and redox homeostasis. We showed that CD90 silence restricted the glucose uptake by ASCs and thus disrupted their PPP and anti-oxidant system, resulting in ASC senescence. Notably, fibroblast growth factor 21 (FGF21) treatment significantly reduced the senescent phenotypes of ASCs by augmenting CD90 protein via glycosylation, which promoted glucose influx via the AKT-GLUT4 axis and therefore mitigated ROS overload. For diet-induced obese mice, chronic administration of low-dose FGF21 relieved their visceral white adipose tissue (VAT) dysfunction and systemic metabolic disorders. In particular, VAT homeostasis was restored in FGF21-treated obese mice, where ASC repertoire was markedly recovered, accompanied by CD90 elevation and anti-senescent phenotypes in these ASCs. Collectively, we reveal a molecular mechanism of ASC senescence by which CD90 downregulation interferes glucose influx into PPP and re

Evidence level

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

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