Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice
| Autor: | Wilma T. Steegenga, Carolien Lute, Evi Andriyani, Joris Deelen, Mark V. Boekschoten, Michael Müller, Fenni Rusli, Erik B. van den Akker, Marian Beekman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Aging FGF21 Peroxisome proliferator-activated receptor Fibroblast growth factor medicine.disease_cause Transcriptome Voeding Metabolisme en Genomica 0302 clinical medicine Non-alcoholic Fatty Liver Disease Gene Regulatory Networks Human Nutrition & Health chemistry.chemical_classification Multidisciplinary Humane Voeding & Gezondheid Fatty liver Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Metabolism and Genomics Up-Regulation Liver Lipotoxicity Metabolisme en Genomica Nutrition Metabolism and Genomics Signal Transduction medicine.medical_specialty NF-E2-Related Factor 2 Down-Regulation 030209 endocrinology & metabolism Biology Article 03 medical and health sciences Voeding Downregulation and upregulation Internal medicine medicine Animals Life Science PPAR alpha VLAG Nutrition nutritional and metabolic diseases Lipid Metabolism medicine.disease digestive system diseases Diet Fibroblast Growth Factors Mice Inbred C57BL PPAR gamma 030104 developmental biology Endocrinology chemistry Oxidative stress Genes Neoplasm |
| Zdroj: | Scientific Reports 6 (2016) Sci Rep Scientific Reports, 6 Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24 and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancer-related pathways. The up-regulated Fgf21 levels in NAFLD were implied to be a protective response against the NAFLD-induced adverse effects, e.g. lipotoxicity, oxidative stress and endoplasmic reticulum stress. An in vivo PPARα challenge demonstrated the dysregulation of PPARα signalling in the presence of NAFLD, which resulted in a stochastically increasing hepatic expression of Fgf21. Notably, elevated plasma Fgf21 was associated with declining expression of Klb, Fgf21’s crucial co-receptor, which suggests a resistance to Fgf21. Therefore, although liver fat accumulation is a benign stage of NAFLD, the elevated plasma Fgf21 likely indicated vulnerability to metabolic stressors that may contribute towards progression to end-stage NAFLD. In conclusion, plasma levels of Fgf21 reflect liver fat accumulation and dysregulation of metabolic pathways in the liver. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|