Shaligram Sharma1, Taylor Dixon1, Sean Jung1, Emily C Graff2, Laura A Forney3, Thomas W Gettys3, Desiree Wanders1. 1. Department of Nutrition, Georgia State University, Atlanta, Georgia, USA. 2. Department of Pathobiology, Auburn University, Auburn, Alabama, USA. 3. Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Abstract
OBJECTIVE: Methionine restriction (MR) decreases inflammation and improves markers of metabolic disease in rodents. MR also increases hepatic and circulating concentrations of fibroblast growth factor 21 (FGF21). Emerging evidence has suggested that FGF21 exerts anti-inflammatory effects. The purpose of this study was to determine the role of FGF21 in mediating the MR-induced reduction in inflammation. METHODS: Wild-type and Fgf21-/- mice were fed a high-fat (HF) control or HF-MR diet for 8 weeks. In a separate experiment, mice were fed a HF diet (HFD) for 10 weeks. Vehicle or recombinant FGF21 (13.6 µg/d) was administered via osmotic minipump for an additional 2 weeks. Inflammation and metabolic parameters were measured. RESULTS: Fgf21-/- mice were more susceptible to HFD-induced inflammation, and MR reduced inflammation in white adipose tissue (WAT) and liver of Fgf21-/- mice. MR downregulated activity of signal transducer and activator of transcription 3 in WAT of both genotypes. FGF21 administration reduced hepatic lipids and blood glucose concentrations. However, there was little effect of FGF21 on inflammatory gene expression in liver or adipose tissue or circulating cytokines. CONCLUSIONS: MR reduces inflammation independent of FGF21 action. Endogenous FGF21 is important to protect against the development of HFD-induced inflammation in liver and WAT, yet administration of low-dose FGF21 has little effect on markers of inflammation.
OBJECTIVE:Methionine restriction (MR) decreases inflammation and improves markers of metabolic disease in rodents. MR also increases hepatic and circulating concentrations of fibroblast growth factor 21 (FGF21). Emerging evidence has suggested that FGF21 exerts anti-inflammatory effects. The purpose of this study was to determine the role of FGF21 in mediating the MR-induced reduction in inflammation. METHODS: Wild-type and Fgf21-/- mice were fed a high-fat (HF) control or HF-MR diet for 8 weeks. In a separate experiment, mice were fed a HF diet (HFD) for 10 weeks. Vehicle or recombinant FGF21 (13.6 µg/d) was administered via osmotic minipump for an additional 2 weeks. Inflammation and metabolic parameters were measured. RESULTS:Fgf21-/- mice were more susceptible to HFD-induced inflammation, and MR reduced inflammation in white adipose tissue (WAT) and liver of Fgf21-/- mice. MR downregulated activity of signal transducer and activator of transcription 3 in WAT of both genotypes. FGF21 administration reduced hepatic lipids and blood glucose concentrations. However, there was little effect of FGF21 on inflammatory gene expression in liver or adipose tissue or circulating cytokines. CONCLUSIONS: MR reduces inflammation independent of FGF21 action. Endogenous FGF21 is important to protect against the development of HFD-induced inflammation in liver and WAT, yet administration of low-dose FGF21 has little effect on markers of inflammation.
Authors: Saverio Cinti; Grant Mitchell; Giorgio Barbatelli; Incoronata Murano; Enzo Ceresi; Emanuela Faloia; Shupei Wang; Melanie Fortier; Andrew S Greenberg; Martin S Obin Journal: J Lipid Res Date: 2005-09-08 Impact factor: 5.922
Authors: Christian Schlein; Saswata Talukdar; Markus Heine; Alexander W Fischer; Lucia M Krott; Stefan K Nilsson; Martin B Brenner; Joerg Heeren; Ludger Scheja Journal: Cell Metab Date: 2016-02-04 Impact factor: 27.287
Authors: Michaela Tencerova; Myriam Aouadi; Pranitha Vangala; Sarah M Nicoloro; Joseph C Yawe; Jessica L Cohen; Yuefei Shen; Lorena Garcia-Menendez; David J Pedersen; Karen Gallagher-Dorval; Richard A Perugini; Olga T Gupta; Michael P Czech Journal: FASEB J Date: 2015-03-24 Impact factor: 5.191
Authors: Mario Ost; Verena Coleman; Anja Voigt; Evert M van Schothorst; Susanne Keipert; Inge van der Stelt; Sebastian Ringel; Antonia Graja; Thomas Ambrosi; Anna P Kipp; Martin Jastroch; Tim J Schulz; Jaap Keijer; Susanne Klaus Journal: Mol Metab Date: 2015-11-24 Impact factor: 7.422
Authors: Clea Bárcena; Pedro M Quirós; Sylvère Durand; Pablo Mayoral; Francisco Rodríguez; Xurde M Caravia; Guillermo Mariño; Cecilia Garabaya; María Teresa Fernández-García; Guido Kroemer; José M P Freije; Carlos López-Otín Journal: Cell Rep Date: 2018-08-28 Impact factor: 9.423
Authors: Jing Xu; David J Lloyd; Clarence Hale; Shanaka Stanislaus; Michelle Chen; Glenn Sivits; Steven Vonderfecht; Randy Hecht; Yue-Sheng Li; Richard A Lindberg; Jin-Long Chen; Dae Young Jung; Zhiyou Zhang; Hwi-Jin Ko; Jason K Kim; Murielle M Véniant Journal: Diabetes Date: 2008-10-07 Impact factor: 9.461
Authors: Diana Cooke; Dwight Mattocks; Sailendra N Nichenametla; Rea P Anunciado-Koza; Robert A Koza; Gene P Ables Journal: Obesity (Silver Spring) Date: 2020-04-29 Impact factor: 5.002