Betaine recovers hypothalamic neural injury by inhibiting astrogliosis and inflammation in fructose-fed rats

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-kappaB (TLR4/NF-kappaB) pathway and histone deacetylases (HDAC3) expression were evaluated. The reduction of pro-opiomelanocortin (POMC) and melanocortin 4 receptor (Mc4R) neurons in fructose-fed rats were ameliorated by betaine. Moreover, fructose induced astrogliosis and proinflammatory cytokines by increasing TLR4, MyD88 and NF-kappaB expression in rat hypothalamus and astrocytes. HDAC3 over-expression preserved the prolonged inflammation in fructose-stimulated astrocytes by regulating nuclear NF-kappaB-dependent transcription. Betaine suppressed TLR4/NF-kappaB 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-kappaB pathway activation and HDAC3 expression to protect against hypothalamic neural injury, which, at least partly, contributes to the improvement on fructose-induced metabolic syndrome.

Li, J.M., et al., Betaine recovers hypothalamic neural injury by inhibiting astrogliosis and inflammation in fructose-fed rats. Mol Nutr Food Res, 2014