Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice

• Published in: Laboratory investigation Vol. 89; no. 9; pp. 1043 - 1052
• Main Authors: Shu, Run-Zhe, Zhang, Feng, Wang, Fang, Feng, De-Chun, Li, Xi-Hua, Ren, Wei-Hua, Wu, Xiao-Lin, Yang, Xue, Liao, Xiao-Dong, Huang, Lei, Wang, Zhu-Gang
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2009; Nature Publishing Group
• Subjects: Adiponectin - deficiency; Adiponectin - genetics; Adiponectin - metabolism; Animals; Biological and medical sciences; Biotechnology; Cell Proliferation; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatectomy; hepatic steatosis; Hepatocytes - metabolism; Investigative techniques, diagnostic techniques (general aspects); knockout mice; Lipid Metabolism - genetics; Liver - metabolism; Liver - pathology; Liver - surgery; Liver Regeneration - physiology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Mice; Mice, Knockout; Other diseases. Semiology; partial hepatectomy; Phosphorylation; PPARα; Socs3; STAT3; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - metabolism; Transcription, Genetic; Transcriptional Activation; partial hepatectomy; Socs3; knockout mice; cell proliferation; STAT3; PPARα; hepatic steatosis; Cell proliferation; Biotechnology; Phosphorylation; Liver; Hepatic disease; Adiponectin; Hepatectomy; PPAR-α receptor; Fatty liver; Partial; Clinical biology; Transcription factor STAT3; Digestive system; Deficiency; Suppressor of cytokine signaling 3; Regeneration; Animal; Knockout mouse; Digestive diseases; Suppressor of cytokine signalling
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2009.63

Liver regeneration is a very complex and well-orchestrated process associated with signaling cascades involving cytokines, growth factors, and metabolic pathways. Adiponectin is an adipocytokine secreted by mature adipocytes, and its receptors are widely distributed in many tissues, including the liver. Adiponectin has direct actions in the liver with prominent roles to improve hepatic insulin sensitivity, increase fatty acid oxidation, and decrease inflammation. To test the hypothesis that adiponectin is required for normal progress of liver regeneration, 2/3 partial hepatectomy (PH) was performed on wild-type and adiponectin-null mice. Compared to wild-type mice, adiponectin-null mice displayed decreased liver mass regrowth, impeded hepatocyte proliferation, and increased hepatic lipid accumulation. Gene expression analysis revealed that adiponectin regulated the gene transcription related to lipid metabolism. Furthermore, the suppressed hepatocyte proliferation was accompanied with reduced signal transducer and activator of transcription protein 3 (STAT3) activity and enhanced suppressor of cytokine signaling 3 (Socs3) transcription. In conclusion, adiponectin-null mice exhibit impaired liver regeneration and increased hepatic steatosis. Increased expression of Socs3 and subsequently reduced activation of STAT3 in adiponectin-null mice may contribute to the alteration of the liver regeneration capability and hepatic lipid metabolism after PH.