Jian-Mei Li, Chen-Xu Ge, Min-Xuan Xu
Scope: Hypothalamic astrogliosis and inflammation cause neural injury, playing a critical role in metabolic syndrome development. This study investigated whether and how fructose caused hypothalamic astrogliosis and inflammation in vivo and in vitro. The inhibitory effects of betaine on hypothalamic neural injury, astrogliosis, and inflammation were explored to address its improvement of fructose-induced metabolic syndrome.
Methods and results: Rats or astrocytes were exposed to fructose and then treated with betaine. Neural injury, proinflammatory markers, Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway, and histone deacetylases 3 (HDAC3) expressions were evaluated. The reduction of pro-opiomelanocortin and melanocortin 4 receptor positive neurons in fructose-fed rats was ameliorated by betaine. Moreover, fructose induced astrogliosis and proinflammatory cytokine production by increasing TLR4, MyD88 (where MyD88 is myeloid differentiation factor 88), and NF-κB expression in rat hypothalamus and astrocytes. HDAC3 overexpression preserved the prolonged inflammation in fructose-stimulated astrocytes by regulating nuclear NF-κB-dependent transcription. Betaine suppressed TLR4/NF-κB pathway activation and HDAC3 expression, contributing to its inhibition of hypothalamic astrogliosis and inflammation in animal and cell models.
Conclusion: These findings suggest that betaine inhibits fructose-caused astrogliosis and inflammation by the suppression of TLR4/NF-κB pathway activation and HDAC3 expression to protect against hypothalamic neural injury, which, at least partly, contributes to the improvement of fructose-induced metabolic syndrome.
Keywords: Astrogliosis; Betaine; Fructose intake; Metabolic syndrome; Neuroinflammation.