Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action.

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.

Use of H2(18)O2 to measure absolute rates of dark H2O2 production in freshwater systems.

Photochemical production is usually considered to be the main source of H2O2 in freshwater systems; here we show that significant dark production also occurs. We used isotope-labeled H2O2 as a tracer to simultaneously determine H2O2 production and decay rates in incubations of unfiltered water samples. Our new technique for H2(18)O2 analysis, requiring only small sample volumes and simple field equipment, allows for preservation of samples in remote locations, followed by gas chromatography mass spectrometry (GCMS) analysis up to six days later. Dark H2O2 production rates of 29-122 nM/h were observed in several lakewater samples. Measured production and decay rates were consistent with pseudo steady-state, early morning [H2O2] measurements made in each water body. Dark H2O2 production is likely to be more important than photochemical production for the total H2O2 budget over 24 h in the freshwater systems we examined. Our results imply that processes usually assumed to be photochemically induced in freshwaters, such as metal redox cycling mediated by H2O2 and O2(-), and production of strong oxidants from the reaction of H2O2 with Fe(II) (Fenton's reaction) could also be occurring at significant rates in the absence of light.