title: Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway.
abstract: OBJECTIVE
  Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms.
  
  
  METHODS
  High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca(2+)/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated.
  
  
  RESULTS
  Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway.
  
  
  CONCLUSIONS
  These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.
authors.affiliation: Department of Pharmacology, Medical School, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Youli
authors.initials: Y
authors.lastname: Xi
authors.forename: Miaozong
authors.initials: M
authors.lastname: Wu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Siqi
authors.initials: S
authors.lastname: Dong
authors.forename: Erfei
authors.initials: E
authors.lastname: Luo
authors.forename: Mingbo
authors.initials: M
authors.lastname: Gu
authors.forename: Xiao
authors.initials: X
authors.lastname: Shen
authors.forename: Yabo
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
chemical_list: D005419:Flavonoids; D014280:Triglycerides; C038044:baicalin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase