Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse.

Lu-Qiong Cai, Xiu-Chun Li, Yang-Yue Wang, Yu-Xin Chen, Xia-Yan Zhu, Zi-Yi Zuo, Yi-Qun Si-Ma, Yi-Nuo Lin, Xiao-Kun Li, Xiao-Ying Huang

Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China. · pubmed

Paper

Abstract

Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.

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Research summary

The paper investigates the role of FGF21 in aging, specifically its involvement in metabolic and inflammatory disorders, which are key aspects of the aging process. By demonstrating how FGF21 deficiency leads to increased inflammation and metabolic dysregulation in aging mice, the study contributes to understanding the mechanisms underlying aging and potential interventions. However, while the findings are solid, they do not present a major breakthrough or transformative implications for the field, thus warranting a moderate impact score.

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