PMID- 35847588 OWN - NLM STAT- MEDLINE DCOM- 20220719 LR - 20220719 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2022 DP - 2022 TI - Fibroblast Growth Factor 19 Improves LPS-Induced Lipid Disorder and Organ Injury by Regulating Metabolomic Characteristics in Mice. PG - 9673512 LID - 10.1155/2022/9673512 [doi] LID - 9673512 AB - Sepsis is extremely heterogeneous pathology characterized by complex metabolic changes. Fibroblast growth factor 19 (FGF19) is a well-known intestine-derived inhibitor of bile acid biosynthesis. However, it is largely unknown about the roles of FGF19 in improving sepsis-associated metabolic disorder and organ injury. In the present study, mice were intravenously injected recombinant human FGF19 daily for 7 days followed by lipopolysaccharide (LPS) administration. At 24 hours after LPS stimuli, sera were collected for metabolomic analysis. Ingenuity pathway analysis (IPA) network based on differential metabolites (DMs) was conducted. Here, metabolomic analysis revealed that FGF19 pretreatment reversed the increase of LPS-induced fatty acids. IPA network indicated that altered linoleic acid (LA) and gamma-linolenic acid (GLA) were involved in the regulation of oxidative stress and mitochondrial function and were closely related to reactive oxygen species (ROS) generation. Further investigation proved that FGF19 pretreatment decreased serum malondialdehyde (MDA) levels and increased serum catalase (CAT) levels. In livers, FGF19 suppressed the expression of inducible NO synthase (iNOS) and enhanced the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and hemeoxygenase-1 (HO-1). Finally, FGF19 pretreatment protected mice against LPS-induced liver, ileum, and kidney injury. Taken together, FGF19 alleviates LPS-induced organ injury associated with improved serum LA and GLA levels and oxidative stress, suggesting that FGF19 might be a promising target for metabolic therapy for sepsis. CI - Copyright (c) 2022 Tiantian Liu et al. FAU - Liu, Tiantian AU - Liu T AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. FAU - Tang, Xiaomeng AU - Tang X AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. FAU - Cui, Yun AU - Cui Y AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Critical Care, Shanghai Jiao Tong University, 200062 Shanghai, China. FAU - Xiong, Xi AU - Xiong X AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Critical Care, Shanghai Jiao Tong University, 200062 Shanghai, China. FAU - Xu, Yaya AU - Xu Y AD - Department of Pediatric Critical Care Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092 Shanghai, China. FAU - Hu, Shaohua AU - Hu S AD - Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. FAU - Feng, Shuyun AU - Feng S AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. FAU - Shao, Lujing AU - Shao L AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. FAU - Ren, Yuqian AU - Ren Y AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Critical Care, Shanghai Jiao Tong University, 200062 Shanghai, China. FAU - Miao, Huijie AU - Miao H AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Critical Care, Shanghai Jiao Tong University, 200062 Shanghai, China. FAU - Zhang, Hong AU - Zhang H AD - Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. FAU - Zhu, Xiaodong AU - Zhu X AD - Department of Pediatric Critical Care Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092 Shanghai, China. FAU - Zhang, Yucai AU - Zhang Y AUID- ORCID: 0000-0002-4905-3600 AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Critical Care, Shanghai Jiao Tong University, 200062 Shanghai, China. FAU - Wang, Chunxia AU - Wang C AUID- ORCID: 0000-0003-4550-5208 AD - Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. AD - Institute of Pediatric Critical Care, Shanghai Jiao Tong University, 200062 Shanghai, China. AD - Clinical Research Unit, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, 200062 Shanghai, China. LA - eng PT - Journal Article DEP - 20220706 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Lipopolysaccharides) RN - 0 (Reactive Oxygen Species) RN - 62031-54-3 (Fibroblast Growth Factors) SB - IM MH - Animals MH - Fibroblast Growth Factors/metabolism MH - Humans MH - *Lipopolysaccharides/metabolism MH - Mice MH - Oxidative Stress MH - Reactive Oxygen Species/metabolism MH - *Sepsis PMC - PMC9279090 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/07/19 06:00 MHDA- 2022/07/20 06:00 PMCR- 2022/07/06 CRDT- 2022/07/18 04:18 PHST- 2022/04/03 00:00 [received] PHST- 2022/05/31 00:00 [revised] PHST- 2022/06/07 00:00 [accepted] PHST- 2022/07/18 04:18 [entrez] PHST- 2022/07/19 06:00 [pubmed] PHST- 2022/07/20 06:00 [medline] PHST- 2022/07/06 00:00 [pmc-release] AID - 10.1155/2022/9673512 [doi] PST - epublish SO - Oxid Med Cell Longev. 2022 Jul 6;2022:9673512. doi: 10.1155/2022/9673512. eCollection 2022.