Jejunal long noncoding RNAs are associated with glycemic control via gut-brain axis after bariatric surgery in diabetic mice.
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.
['Liang|Yongjun|Y|', 'Yu|Bo|B|', 'Wang|Yueqian|Y|', 'Qiao|Zhengdong|Z|', 'Cao|Ting|T|', 'Zhang|Peng|P|']
D000818:Animals D050110:Bariatric Surgery D001786:Blood Glucose D001921:Brain D003921:Diabetes Mellitus, Experimental D003924:Diabetes Mellitus, Type 2 D059305:Diet, High-Fat D015536:Down-Regulation D004386:Duodenum D063990:Gene Ontology D016678:Genome D007583:Jejunum D008810:Mice, Inbred C57BL D046228:Microarray Analysis D018377:Neurotransmitter Agents D011184:Postoperative Period D062085:RNA, Long Noncoding D012333:RNA, Messenger D011897:Random Allocation D014157:Transcription Factors
Metabolic and bariatric surgery lncRNAs Microarray Gut–brain axis Type 2 diabetes (T2D)