Metformin regulates hepatic lipid metabolism through activating AMP-activated protein kinase and inducing ATGL in laying hens.

Abstract

Although many clinical trials have showed that metformin improves non-alcoholic fatty liver disease, which is a common liver disease associated with hepatic enzyme abnormalities, an animal model is required to investigate the effects of altered gene expression and post-translational processing (proteins) in mediating the observed responses. Laying hens appear to develop fatty livers, as in the case in human beings, when ingesting energy in excess of maintenance, and they can be used as an animal model for observing hepatic steatosis. The aim of this study was to investigate whether metformin could improve the non-alcoholic fatty liver of laying hens and to examine the possible mechanisms of lipid-lowering effects. Forty-eight Leghorn laying hens of Hy-Line variety W-36 - 44 weeks with 64.8% hen-day egg production - were randomly assigned into 4 treatments, each receiving 0, 10, 30, or 100mg of metformin with saline per kg body weight by daily wing vein injection. Results showed that, compared with the control, significant decreases existed in the laying rates; plasma triglyceride, cholesterol, and insulin levels; body weights; abdominal fat weights; hepatic lipid contents; and hepatic fatty acid synthase expression of layers receiving 30 or 100mg per kg body weight, whereas significant increases in their hepatic 5'adenosine monophosphate-activated protein kinase, acyl-CoA carboxylase phosphorylation, adipose triglyceride lipase, and carnitine palmitoyl transferase-1 expression were observed. These data suggest that metformin could reduce lipid deposits in the liver and that the laying hen is a valuable animal model for studying hepatic steatosis.

• Authors: Wei-Lu Chen, Hen-Wei Wei, Wen-Zan Chiu, Ching-Hui Kang, Ting-Han Lin, Chien-Ching Hung, Ming-Chun Chen, Ming-Song Shieh, Chin-Cheng Lee, Horng-Mo Lee
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 671 Issue 1-3 Pg. 107-12 (Dec 05 2011) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 21958877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Fatty Acids, Nonesterified
• Hypolipidemic Agents
• Metformin
• AMP-Activated Protein Kinases
• Lipase

Topics

• AMP-Activated Protein Kinases (metabolism)
• Abdominal Fat (cytology, drug effects)
• Animals
• Body Weight (drug effects)
• Chickens
• Eating (drug effects)
• Enzyme Activation (drug effects)
• Enzyme Induction (drug effects)
• Fatty Acids, Nonesterified (metabolism)
• Female
• Gene Expression Regulation (drug effects)
• Hyperlipidemias (drug therapy)
• Hypolipidemic Agents (pharmacology, therapeutic use)
• Lipase (biosynthesis)
• Lipid Metabolism (drug effects, genetics)
• Liver (drug effects, enzymology, metabolism)
• Metformin (pharmacology, therapeutic use)
• Oviposition (drug effects)
• Phosphorylation (drug effects)