title: Metabolomics Analysis Revealed Distinct Cyclic Changes of Metabolites Altered by Chronic Ethanol-Plus-Binge and Shp Deficiency.
abstract: Chronic ethanol (EtOH) consumption causes alcoholic liver disease (ALD), and disruption of the circadian system facilitates the development of ALD. Small heterodimer partner (SHP) is a nuclear receptor and critical regulator of hepatic lipid metabolism. This study aimed at depicting circadian metabolomes altered by chronic EtOH-plus-binge and Shp deficiency using high-throughput metabolomics.
  
  
  
  Wild-type (WT) C57BL/6 and Shp-/-mice were fed the control diet (CD) or Lieber-DeCarli EtOH liquid diet (ED) for 10 days followed by a single bout of maltose (CD + M) or EtOH (ED + E) binge on the 11th day. Serum and liver were collected over a 24-hour light/dark (LD) cycle at Zeitgeber time ZT12, ZT18, ZT0, and ZT6, and metabolomics was performed using gas chromatography-mass spectrometry.
  
  
  
  A total of 110 metabolites were identified in liver and of those 80 were also present in serum from pathways of carbohydrates, lipids, pentose phosphate, amino acids, nucleotides, and tricarboxylic acid cycle. In the liver, 91% of metabolites displayed rhythmicity with ED + E, whereas in the serum, only 87% were rhythmic. Bioinformatics analysis identified unique metabolome patterns altered in WT CD + M, WT ED + E, Shp-/-CD + M, and Shp-/-ED + E groups. Specifically, metabolites from the nucleotide and amino acid pathway (ribose, glucose-6-phosphate, glutamic acid, aspartic acid, and sedoheptulose-7-P) were elevated in Shp-/-CD + M mice during the dark cycle, whereas metabolites including N-methylalanine, 2-hydroxybutyric acid, and 2-hydroxyglutarate were elevated in WT ED + E mice during the light cycle. The rhythmicity and abundance of other individual metabolites were also significantly altered by both control and EtOH diets.
  
  
  
  Metabolomics provides a useful means to identify unique metabolites altered by chronic EtOH-plus-binge.
authors: Department of Physiology and Neurobiology, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut.
authors: Melanie
authors: M
authors: Tran
authors: Department of Physiology and Neurobiology, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut.|Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
authors: Zhihong
authors: Z
authors: Yang
authors: Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.|Roudebush Veterans Administration Medical Center, Indianapolis, Indiana.
authors: Suthat
authors: S
authors: Liangpunsakul
authors: Department of Physiology and Neurobiology, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut.|Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.|Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut.|School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Li
authors: L
authors: Wang
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000097:blood / Q000378:metabolism*; D002940:Circadian Rhythm / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D051379:Mice; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D000431:Ethanol
keywords: Alcohol; Circadian Clock; Metabolomics; Nuclear Receptor