Microglial polarization and the subsequent neuroinflammatory response were identified as key contributors to the progress of Parkinson's disease (PD). Researchers have shown that fibroblast growth factor 21 (FGF21) plays multiple biological functions, including anti-inflammation and neuroprotection. However, the knowledge of FGF21 on microglial polarization in PD in vivo is far from completion. In this study, both in vivo and in vitro models were used to investigate whether FGF21 enhances the brain function by modulating microglial polarization in PD. The protective effects of FGF21 in vivo were conducted using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice model alongside intraperitoneally received FGF21. A behavioral test battery and tyrosine hydroxylase (TH) immunohistochemistry were conducted to evaluate the neuronal function and nigrostriatal tract integrity. Immunofluorescence assay and Western blot were used to examine M1/M2 microglial polarization. Then, a microglia-neuron co-culture system was adopted in vitro to identify the underlying molecular mechanisms of FGF21. The results showed that FGF21 significantly alleviated motor and cognitive impairment in mice with PD. FGF21 also protected TH-positive neuron cells in the striatum and midbrain. Mechanistically, FGF21 suppressed M1 microglial polarization and the subsequent mRNA expression of pro-inflammatory factors while promoting M2 microglial polarization with increasing anti-inflammatory factors in mice with PD. Furthermore, sirtuin 1 (SIRT1) and the nuclear factor-kappa B (NF-κB) pathway were involved in the FGF21-induced M2 microglial polarization. Conversely, SIRT1 inhibitor EX527 significantly prevented both the FGF21-induced SIRT1 expression and M2 microglial polarization. Moreover, FGF21 pretreatment of microglia significantly prevented neuronal cell apoptosis in a microglia-neuron co-culture system. In conclusion, our data demonstrate that FGF21 exerted its protective effects in the pathology of PD through SIRT1/NF-κB pathway-mediated microglial polarization. Given the safety record of human clinical trials, FGF21 could be a promising therapy for clinical trials to ameliorate motor and nonmotor deficits in patients with PD.

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Herein, a fast and visible colorimetric method for bisphenol A (BPA) detection was developed using hemin-functionalized reduced graphene oxide (H–rGO) composites and aptamer.

Sex differences in obesity have been well established, but the metabolic mechanism underlying these differences remains unclear. In the present study, we determined the expression levels of endogenous fibroblast growth factor 21 (FGF21) and its related receptors in male and female mice that were fed a high-fat diet (HFD) for 12 weeks. We also analyzed the metabolic changes in serum and livers using a nuclear magnetic resonance-based metabolomics approach. Reverse transcription polymerase chain reaction and western blotting results revealed that the levels of FGFR1, FGFR2, and co-factor β-klotho were upregulated in female mice to alleviate FGF21 resistance induced by HFD. The metabolomics results demonstrated that the serum and liver metabolic patterns of HFD-fed male mice were significantly separated from those of the female HFD-fed group and the normal diet group. Furthermore, low-density lipoprotein/very low density lipoprotein and betaine levels were associated with the resistance of exogenous HFD in female mice. These findings imply that sex-based differences in metabolism and susceptibility to obesity might be mediated by the FGF21 signaling pathway.

Diabetic enteropathy (DE) is a diabetic complication and affects the quality of life for which there are limited therapies. In this study, db/db mice were administered with a basic fibroblast growth factor (bFGF) to explore its therapeutic effect on the intestine. 1H NMR-based metabolomics was applied to investigate the metabolic pattern. H&E and PAS staining were used to observe the morphological phenotypes related to intestinal barrier function. Tight junction proteins such as Zo-1 and Occluding were successively tested by immunofluorescence and real-time PCR. We found that bFGF treatment significantly restored intestinal barrier function. In addition, the administration of bFGF decreased the levels of inflammatory cytokines in the cecum. Metabolomic results show that bFGF remodeled metabolic phenotypes of the colon, cecum, and small intestine in db/db mice, including energy metabolism, short chain fatty acid metabolism, amino acid metabolism, and choline metabolism. Hence, this study indicates that the bFGF has a protective effect in diabetic bowel disease by restoring intestinal barrier function, reducing inflammatory infiltration, and remodeling metabolic function.