title: Betaine recovers hypothalamic neural injury by inhibiting astrogliosis and inflammation in fructose-fed rats.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Li
authors.forename: Chen-Xu
authors.initials: CX
authors.lastname: Ge
authors.forename: Min-Xuan
authors.initials: MX
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Yu
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Fan
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D000818:Animals; D001622:Betaine / Q000494:pharmacology*; D005632:Fructose / Q000009:adverse effects*; D005786:Gene Expression Regulation; D005911:Gliosis / Q000188:drug therapy* / Q000473:pathology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D007027:Hypothalamic Diseases / Q000188:drug therapy* / Q000473:pathology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D001622:Betaine; D005632:Fructose; D006655:Histone Deacetylases; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D000099186:Histone Deacetylase 3; C507781:Myd88 protein, rat; C495347:Tlr4 protein, rat
keywords: Astrogliosis; Betaine; Fructose intake; Metabolic syndrome; Neuroinflammation