Intracellular mechanisms underlying lipid accumulation (white opaque substance) in gastric epithelial neoplasms: A pilot study of expression profiles of lipid-metabolism-associated genes.

Abstract

BACKGROUND AND AIM:

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.

CONCLUSION:

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: Munechika Enjoji, Motoyuki Kohjima, Kensei Ohtsu, Kazuhisa Matsunaga, Yusuke Murata, Makoto Nakamuta, Kentaro Imamura, Hiroshi Tanabe, Akinori Iwashita, Takashi Nagahama, Kenshi Yao
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 31 Issue 4 Pg. 776-81 (Apr 2016) ISSN: 1440-1746 [Electronic] Australia
• PMID: 26513060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Perilipin-2

Topics

• Aged
• Aged, 80 and over
• Down-Regulation
• Female
• Gastric Mucosa
• Humans
• Lipid Droplets (metabolism)
• Lipid Metabolism (genetics)
• Lipogenesis (genetics)
• Lipolysis (genetics)
• Male
• Middle Aged
• Mitochondria (metabolism)
• Neoplasms, Glandular and Epithelial (genetics, metabolism)
• Oxidation-Reduction
• Oxidative Stress
• Perilipin-2 (metabolism)
• Pilot Projects
• Stomach Neoplasms (genetics, metabolism)
• Transcriptome