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Chito-Oligosaccharide Inhibits the De-Methylation of a CpG Island within the Leptin (LEP) Promoter during Adipogenesis of 3T3-L1 Cells
Date Issued
27 March 2013
Date Available
20T12:00:52Z April 2015
Abstract
Chito-oligosaccharide (COS) is a natural bioactive compound, which has been shown to suppress lipid metabolic genes and lipid accumulation in differentiating adipocytes. Leptin has been identified as a key regulator of energy homeostasis and is known to be under epigenetic regulation during adipogenesis. Hence, the first objective of this experiment was to compare leptin gene (LEP) expression and leptin secretion during the different stages of adipogenesis and to investigate the effect of COS on these processes. As COS inhibited LEP expression during adipogenesis, the second aim was to investigate the methylation dynamics of a ¿CpG¿ island in the proximal region of the LEP promoter during adipogenesis and to determine the effect of COS on this process. Mouse 3T3-L1 cells were stimulated to differentiate in the absence or presence of COS and the levels of leptin mRNA and protein were evaluated on days 0, 2, 4 and 6 post-induction of differentiation (PID). The extent of de-methylation of six CpG sites was evaluated. LEP mRNA transcript and protein could not be detected on either day 0PID or 2PID. In contrast, both were detected on day 4PID (P<0.05) and 6PID (P<0.001) and both were inhibited by COS (P<0.001). Of the six CpG sites analyzed, CpG_52, CpG_62 and CpG_95 became 11.5, 5.0 and 5.0% de-methylated between day 2PID and 6PID, respectively. COS blocked this de-methylation event at CpG_52 (P<0.001), CpG_62 (P<0.01) and CpG_95 (P<0.01) on day 6PID. These data suggest that COS can have an epigenetic effect on differentiating adipocytes, a novel biological function of COS which has potential applications for the manipulation of leptin gene expression, adipogenesis, and conditions within the metabolic syndrome spectrum.
Sponsorship
Department of Agriculture, Food and the Marine
Other Sponsorship
Marine Institute
National Development Plan 2007–2013
Type of Material
Journal Article
Publisher
Public Library of Science
Journal
PLoS ONE
Volume
8
Issue
3
Start Page
1
End Page
7
Copyright (Published Version)
2013 the Authors
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
File(s)
Owning collection
Scopus© citations
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