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Open Access 24-04-2024 | Fatty Liver | RESEARCH

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

Authors: 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

Published in: Inflammation

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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Title: Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse
Authors: 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
Publication date: 24-04-2024
Publisher: Springer US
Keyword: Fatty Liver
Published in: Inflammation
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-024-02032-3

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