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

• Published in: European journal of pharmacology Vol. 671; no. 1-3; pp. 107 - 112
• Main Authors: Chen, Wei-Lu, Wei, Hen-Wei, Chiu, Wen-Zan, Kang, Ching-Hui, Lin, Ting-Han, Hung, Chien-Ching, Chen, Ming-Chun, Shieh, Ming-Song, Lee, Chin-Cheng, Lee, Horng-Mo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05.12.2011; Elsevier
• Subjects: abdominal fat; Abdominal Fat - cytology; Abdominal Fat - drug effects; acyl coenzyme A; Adipose triglyceride lipase; AMP-activated protein kinase; AMP-Activated Protein Kinases; AMP-Activated Protein Kinases - metabolism; animal models; Animals; Biological and medical sciences; biosynthesis; body weight; Body Weight - drug effects; carnitine; Chickens; cholesterol; clinical trials; cytology; drug effects; drug therapy; Eating; Eating - drug effects; egg production; energy; Enzyme Activation; Enzyme Activation - drug effects; Enzyme Induction; Enzyme Induction - drug effects; enzymology; Fatty Acids, Nonesterified; Fatty Acids, Nonesterified - metabolism; fatty liver; fatty-acid synthase; Female; Gastroenterology. Liver. Pancreas. Abdomen; gene expression; Gene Expression Regulation; Gene Expression Regulation - drug effects; genetics; humans; Hyperlipidemias; Hyperlipidemias - drug therapy; Hypolipidemic Agents; Hypolipidemic Agents - pharmacology; Hypolipidemic Agents - therapeutic use; insulin; Laying hen; laying hens; Lipase; Lipase - biosynthesis; lipid metabolism; Lipid Metabolism - drug effects; Lipid Metabolism - genetics; liver; Liver - drug effects; Liver - enzymology; Liver - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; metabolism; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Non-alcoholic fatty liver disease; Other diseases. Semiology; Oviposition; Oviposition - drug effects; pharmacology; Pharmacology. Drug treatments; phosphorylation; Phosphorylation - drug effects; proteins; therapeutic use; triacylglycerol lipase; triacylglycerols; Adipose triglyceride lipase; Metformin; Non-alcoholic fatty liver disease; AMP-activated protein kinase; Laying hen; Adipose tissue; Liver; Non-specific serine/threonine protein kinase; Triacylglycerol lipase; Hepatic disease; Lipids; Esterases; Hypoglycemic agent; Biguanides; Aves; AMP; Digestive system; Enzyme; Transferases; Metabolism; Carboxylic ester hydrolases; Vertebrata; Non alcoholic steatohepatitis; Hydrolases; Digestive diseases; Chicken; Pharmacokinetics
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2011.09.029

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 – 44weeks 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.