title: Intracellular mechanisms underlying lipid accumulation (white opaque substance) in gastric epithelial neoplasms: A pilot study of expression profiles of lipid-metabolism-associated genes.
abstract: OBJECTIVE
  White opaque substance (WOS) is a novel endoscopic finding in gastric neoplasms, indicating the intracellular accumulation of lipid droplets (LDs). However, gastric lipid metabolism has not been extensively investigated, even in normal mucosa. We investigated the expression profiles of lipid-metabolism-associated genes in gastric neoplasms.
  
  
  METHODS
  Thirty-four patients with early gastric cancer or adenoma were enrolled in this study. Paired biopsy samples from tumor and adjacent non-tumor areas were obtained and analyzed by real-time polymerase chain reaction. Endoscopically resected specimens were evaluated histopathologically.
  
  
  RESULTS
  Genes associated with β-oxidation (peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1A, and hydroxyacyl-CoA dehydrogenase), lipoprotein excretion (apolipoprotein B, microsomal triglyceride transfer protein, and acyl-CoA:cholesterol acyltransferase 2), fatty acid transport (fatty acid-binding protein), construction of triglycerides in the endoplasmic reticulum (acyl-CoA:diacylglycerol acyltransferase 1), and LD degradation/lipolysis (comparative gene identification-58, adipose triglyceride lipase) were significantly downregulated in neoplasms compared with non-tumor areas. Pyruvate dehydrogenase lipoamide kinase isozyme 4 (negative regulator of glycolysis) and adipophilin (LD surface component) were also repressed. Conversely, expression levels of genes associated with de novo lipogenesis (sterol regulatory element-binding protein 1c, acyl-CoA:diacylglycerol acyltransferase 2) were significantly enhanced in neoplasms. There was no significant difference in gene expression levels between carcinomas and adenomas, or between WOS-positive and WOS-negative neoplasms.
  
  
  CONCLUSIONS
  Gene expression profiles in neoplasms suggest a predominance of lipid storage (lipogenesis/LD formation) over consumption (β-oxidation/excretion/lipolysis). Lipid accumulation and WOS in gastric epithelial neoplasms may be caused by impaired mitochondrial oxidation, lipoprotein excretion, and LD degradation.
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.affiliation: Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.affiliation: Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Ohtsu
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.affiliation: Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Imamura
authors.affiliation: Department of Pathology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanabe
authors.affiliation: Department of Pathology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Iwashita
authors.affiliation: Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagahama
authors.affiliation: Department of Endoscopy, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Yao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015536:Down-Regulation; D005260:Female; D005753:Gastric Mucosa; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics*; D008066:Lipolysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000070780:Perilipin-2 / Q000378:metabolism; D010865:Pilot Projects; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D000070780:Perilipin-2
keywords: fatty acid; gastric cancer; lipid metabolism; triglyceride; white opaque substance