FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation
The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically worldwide and, subsequently, also the risk of developing non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and cancer. Today, weight lo ss is the only available treatment, but administration of fib...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Bioscientifica
2020-08-01
|
| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/9/8/EC-20-0152.xml |
| _version_ | 1818353860517822464 |
|---|---|
| author | Helle Keinicke Gao Sun Caroline M Junker Mentzel Merete Fredholm Linu Mary John Birgitte Andersen Kirsten Raun Marina Kjaergaard |
| author_facet | Helle Keinicke Gao Sun Caroline M Junker Mentzel Merete Fredholm Linu Mary John Birgitte Andersen Kirsten Raun Marina Kjaergaard |
| author_sort | Helle Keinicke |
| collection | DOAJ |
| description | The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically worldwide and, subsequently, also the risk of developing non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and cancer. Today, weight lo ss is the only available treatment, but administration of fibroblast growth factor 21 (FG F21) analogues have, in addition to weight loss, shown improvements on liver metabolic health but the mechanisms behind are not entirely clear. The aim of this study was to investigate the hepatic metabolic profile in response to FGF21 treatment. Diet-i nduced obese (DIO) mice were treated with s.c. administration of FGF21 or subjected to caloric restriction by switching from high fat diet (HFD) to chow to induce 20% weight loss and changes were compared to vehicle dosed DIO mice. Cumulative caloric intake was reduced by chow, while no differences were observed between FGF21 and vehicle dos ed mice. The body weight loss in both treatment groups was associated with reduced body fat mass and hepatic triglycerides (TG), while hepatic cholesterol was slightly decreased by chow. Liver glycogen was decreased by FGF21 and increased by chow. The hepatic gene expression profiles suggest that FGF21 increased uptake of fatty acids and lipoproteins, channeled TGs toward the production of cholesterol and bile acid, reduced lipogenesis and increased hepatic glucose output. Furthermore, FGF21 appeared to reduce i nflammation and regulate hepatic leptin receptor-a expression. In conclusion, F GF21 affected several metabolic pathways to reduce hepatic steatosis and improve hepatic health and markedly more genes than diet restriction (61 vs 16 out of 89 investigated genes). |
| first_indexed | 2024-12-13T19:16:14Z |
| format | Article |
| id | doaj.art-e68e13f481f74afe897403913b097076 |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-12-13T19:16:14Z |
| publishDate | 2020-08-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-e68e13f481f74afe897403913b0970762022-12-21T23:34:16ZengBioscientificaEndocrine Connections2049-36142049-36142020-08-0198755768https://doi.org/10.1530/EC-20-0152FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammationHelle Keinicke0Gao Sun1Caroline M Junker Mentzel2Merete Fredholm3Linu Mary John4Birgitte Andersen5Kirsten Raun6Marina Kjaergaard7Insulin and Device Trial Operations, Novo Nordisk A/S, Søborg, DenmarkPharmacology and Histopathology, Novo Nordisk A/S, ChinaDepartment of Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, DenmarkDepartment of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, DenmarkGlobal Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, DenmarkGlobal Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, DenmarkGlobal Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, DenmarkGlobal Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, DenmarkThe prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically worldwide and, subsequently, also the risk of developing non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and cancer. Today, weight lo ss is the only available treatment, but administration of fibroblast growth factor 21 (FG F21) analogues have, in addition to weight loss, shown improvements on liver metabolic health but the mechanisms behind are not entirely clear. The aim of this study was to investigate the hepatic metabolic profile in response to FGF21 treatment. Diet-i nduced obese (DIO) mice were treated with s.c. administration of FGF21 or subjected to caloric restriction by switching from high fat diet (HFD) to chow to induce 20% weight loss and changes were compared to vehicle dosed DIO mice. Cumulative caloric intake was reduced by chow, while no differences were observed between FGF21 and vehicle dos ed mice. The body weight loss in both treatment groups was associated with reduced body fat mass and hepatic triglycerides (TG), while hepatic cholesterol was slightly decreased by chow. Liver glycogen was decreased by FGF21 and increased by chow. The hepatic gene expression profiles suggest that FGF21 increased uptake of fatty acids and lipoproteins, channeled TGs toward the production of cholesterol and bile acid, reduced lipogenesis and increased hepatic glucose output. Furthermore, FGF21 appeared to reduce i nflammation and regulate hepatic leptin receptor-a expression. In conclusion, F GF21 affected several metabolic pathways to reduce hepatic steatosis and improve hepatic health and markedly more genes than diet restriction (61 vs 16 out of 89 investigated genes).https://ec.bioscientifica.com/view/journals/ec/9/8/EC-20-0152.xmlfibroblast growth factor 21 (fgf21)non-alcoholic fatty liver disease (nafld)lipid metabolismglucose metabolisminflammation |
| spellingShingle | Helle Keinicke Gao Sun Caroline M Junker Mentzel Merete Fredholm Linu Mary John Birgitte Andersen Kirsten Raun Marina Kjaergaard FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation Endocrine Connections fibroblast growth factor 21 (fgf21) non-alcoholic fatty liver disease (nafld) lipid metabolism glucose metabolism inflammation |
| title | FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation |
| title_full | FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation |
| title_fullStr | FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation |
| title_full_unstemmed | FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation |
| title_short | FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation |
| title_sort | fgf21 regulates hepatic metabolic pathways to improve steatosis and inflammation |
| topic | fibroblast growth factor 21 (fgf21) non-alcoholic fatty liver disease (nafld) lipid metabolism glucose metabolism inflammation |
| url | https://ec.bioscientifica.com/view/journals/ec/9/8/EC-20-0152.xml |
| work_keys_str_mv | AT hellekeinicke fgf21regulateshepaticmetabolicpathwaystoimprovesteatosisandinflammation AT gaosun fgf21regulateshepaticmetabolicpathwaystoimprovesteatosisandinflammation AT carolinemjunkermentzel fgf21regulateshepaticmetabolicpathwaystoimprovesteatosisandinflammation AT meretefredholm fgf21regulateshepaticmetabolicpathwaystoimprovesteatosisandinflammation AT linumaryjohn fgf21regulateshepaticmetabolicpathwaystoimprovesteatosisandinflammation AT birgitteandersen fgf21regulateshepaticmetabolicpathwaystoimprovesteatosisandinflammation AT kirstenraun fgf21regulateshepaticmetabolicpathwaystoimprovesteatosisandinflammation AT marinakjaergaard fgf21regulateshepaticmetabolicpathwaystoimprovesteatosisandinflammation |