Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway.

Abstract

BACKGROUND/AIMS:

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.

CONCLUSION:

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: Youli Xi, Miaozong Wu, Hongxia Li, Siqi Dong, Erfei Luo, Mingbo Gu, Xiao Shen, Yabo Jiang, Yaqun Liu, Hua Liu
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 35 Issue 6 Pg. 2349-59 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 25896320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Flavonoids
• Triglycerides
• baicalin
• Aspartate Aminotransferases
• Alanine Transaminase
• Calcium-Calmodulin-Dependent Protein Kinase Kinase
• AMP-Activated Protein Kinases
• Acetyl-CoA Carboxylase

Topics

• AMP-Activated Protein Kinases (metabolism)
• Acetyl-CoA Carboxylase (metabolism)
• Adipose Tissue (drug effects, metabolism)
• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Body Weight (drug effects)
• Calcium-Calmodulin-Dependent Protein Kinase Kinase (metabolism)
• Diet, High-Fat (adverse effects)
• Fatty Liver (blood, drug therapy, metabolism)
• Flavonoids (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Obesity (blood, drug therapy, metabolism)
• Signal Transduction (drug effects)
• Triglycerides (blood)