Abstract
Background
Metabolic and bariatric surgery is effective in ameliorating type 2 diabetes, although
its underlying mechanisms are largely unknown. Our previous study indicated that the
distinctly expressed duodenal long noncoding RNAs (lncRNAs) induced by the duodenal-jejunal
bypass (DJB) might play a role in improving glycemic control via the enteropancreatic
axis. Therefore, the physiologic role of the jejunum in metabolic regulation after
DJB requires investigation.
Objectives
To investigate the alterations in the jejunal Roux limb lncRNA expression signatures
after DJB and analyze the functional pathways associated with metabolic improvement
on a genome-wide scale in high-fat diet–induced diabetic mice.
Setting
University medical center.
Methods
Diabetic mice induced by high-fat diet were randomly assigned into 2 groups undergoing
either DJB or sham surgery. The lncRNA and messenger (m)RNA expression profiles of
the Roux limb segment of the jejunum in both groups were investigated using microarray.
To identify the functional characteristics of the distinctly expressed lncRNAs, gene
ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted.
The lncRNA-mRNA and lncRNA-transcription factor interaction networks were constructed
based on Pearson correlation analysis.
Results
Compared with the sham group, 827 dysregulated (fold change ≥2.0) jejunal lncRNAs
were identified in the DJB group. Both Kyoto Encyclopedia of Genes and Genomes pathway
and gene ontology enrichment analysis revealed that 601 lncRNA–co-expressed mRNAs
(fold change ≥2.0) were associated with neuromodulation-related pathways or biological
processes, including serotonergic, glutamatergic, and dopaminergic synapses. In addition,
hormonal regulation–related pathways, especially steroid biosynthesis, were also enriched.
The results were further confirmed by bioinformatic analysis of target genes or transcription
factors predicted on the basis of dysregulated jejunal lncRNAs. Furthermore, the NONMMUT023781
lncRNA may simultaneously target the Adcy8 mRNA both in cis and in trans and participate
in neuromodulation and hormonal regulation.
Conclusion
Alterations of jejunal Roux limb lncRNA and mRNA expression profiles trigger both
neuromodulation and endocrine-related pathways, which play a critical role in type
2 diabetes remission after metabolic and bariatric surgery via the gut–brain axis.
NONMMTU023781 and Adcy8 were identified as potential targets, which warrant further
research.
Keywords
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Article info
Publication history
Published online: March 08, 2018
Accepted:
March 4,
2018
Received:
December 5,
2017
Footnotes
☆This study was supported by the Shanghai Pudong Key Medical Discipline Construction Project (Grant No. PWZxk2017-16), Pudong Bureau of Health and Family Planning Grants (Grant No. Pw2016 B-18), and Shanghai Pudong Hospital Research Fund (Grant No. 201502).
Identification
Copyright
© 2018 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
