title: Liver Regeneration Is Impaired in Mice with Acute Exposure to a Very Low Carbohydrate Diet.
abstract: The metabolic response to hepatic insufficiency has been implicated in the regulators of normal liver regeneration. Modulation of nutritional factors has been demonstrated to affect liver regeneration. Diets containing very low carbohydrate and high fat levels cause a unique metabolic state, the effect of which on liver regeneration is unknown.
  
  
  
  Mice were placed on standard mice chow (ND) or a very low carbohydrate diet (VLCD) after 70% partial hepatectomy (PH). After 48 h, mice on VLCD were placed back to ND. The serum metabolic profiles, hepatic lipid content, and gene expression profile were examined. The dynamics of liver regeneration were detected at timed points. Activation of signaling pathways was examined.
  
  
  
  VLCD feeding caused hypoglycemia and elevation of serum β-hydroxybutyrate and free fatty acids in mice after PH. It increased hepatic triglyceride contents, enhanced fatty acid oxidation, and reduced lipid synthesis. Mice on VLCD exhibited diminished hepatocellular mitotic frequency, a reduced BrdU incorporation and liver mass regeneration ratio, and delayed expression of PCNA. Expressions of IL-6 and TNFα in liver and serum were downregulated. Meanwhile, phosphorylation of STAT3, Erk, and AKT was delayed compared with controls.
  
  
  
  VLCD feeding delayed liver regeneration, probably because of the suppression of TNFα-IL-6-STAT3 signaling and delayed activation of Erk and AKT induced by the unique metabolic effects of this diet.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, Xuehai Building, Room A315, 101 Longmian Road, Jiangning District, Nanjing, 211166, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, Xuehai Building, Room A315, 101 Longmian Road, Jiangning District, Nanjing, 211166, China.
authors.forename: Yandie
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, Xuehai Building, Room A315, 101 Longmian Road, Jiangning District, Nanjing, 211166, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Sun
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, Xuehai Building, Room A315, 101 Longmian Road, Jiangning District, Nanjing, 211166, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, Xuehai Building, Room A315, 101 Longmian Road, Jiangning District, Nanjing, 211166, China. haoli@njmu.edu.cn.
authors.forename: Hao
authors.identifier: 0000-0002-5965-8283
authors.initials: H
authors.lastname: Li
mesh_terms: D000821:Animal Feed; D000818:Animals; D004032:Diet / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006498:Hepatectomy; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D004040:Dietary Carbohydrates; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: Hepatectomy; Ketogenic diet; Liver regeneration; Low carbohydrate diet; Metabolism