title: Duodenal long noncoding RNAs are associated with glycemic control after bariatric surgery in high-fat diet-induced diabetic mice.
abstract: BACKGROUND
  The duodenum plays a role in the mechanism of type 2 diabetes remission after bariatric surgery. Roux-en-Y gastric bypass (RYGB) may change gene expression in the duodenum and metabolism. Long noncoding RNAs (lncRNAs) constitute a novel class of RNAs that regulate gene expression. Little is known about how duodenal lncRNAs respond to RYGB. Logically, studies on the changes of duodenal lncRNAs potentially can lead to an understanding of the mechanisms of bariatric surgery, as well as discovery of antidiabetic drug targets and biomarkers predicting postoperative outcome.
  
  
  OBJECTIVE
  To investigate the expression signature of duodenal lncRNAs associated with glycemic improvement by duodenal-jejunal bypass (DJB), a component of RYGB, on a genome-wide scale in high-fat diet-induced diabetic mice.
  
  
  METHODS
  University medical center.
  
  
  METHODS
  High fat diet-induced diabetic mice were randomized into 2 groups receiving either the DJB or a sham procedure. Microarray was applied to screen the differentially expressed lncRNAs and messenger RNAs (mRNAs) in the duodenum between the DJB and sham groups, and the result was validated by quantitative real-time polymerase chain reaction in another cohort of animals. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the potential lncRNA functions. Based on Pearson correlation analysis, the lncRNA-mRNA and lncRNA-transcription factor (TF) interaction networks were constructed to identify and rank core regulatory lncRNAs and transcription factors.
  
  
  RESULTS
  A total of 301 lncRNAs, including 232 that were upregulated and 69 downregulated (fold change≥2.0), were differentially expressed in the duodenum between the DJB and sham groups. GO enrichment indicated that these lncRNA-coexpressed mRNAs were correlated with biological processes including cell proliferation, digestion, and catabolic and biosynthetic processes. KEGG pathway analysis revealed that in addition to the digestion and absorption signaling pathways, pancreatic secretion- and inflammatory process-related signaling pathways were mostly enriched in the DJB group. In addition, the lncRNA-mRNA interaction network combined with GO and KEGG pathway analysis suggested that as a top-ranked gene, NONMMUG021726 may play an important role in the mechanism of type 2 diabetes remission after DJB.
  
  
  CONCLUSIONS
  DJB leads to drastic changes in lncRNA and mRNA expressions in the duodenum. The majority of top-ranked lncRNAs and mRNAs have roles in pancreatic secretion and inflammatory processes, implying that bypass of the duodenum may initiate insulin secretion and attenuate inflammation. In addition, modulators of such lncRNAs, most likely NONMMUG021726, have potential to become therapeutic targets or biomarkers for prediction of the outcomes of bariatric surgery.
authors.affiliation: Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Center for Metabolic and Bariatric Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Yueqian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Cao
authors.affiliation: Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China; Center for Metabolic and Bariatric Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China. Electronic address: zhangpg@yahoo.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000601:surgery; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000601:surgery*; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000502:physiology; D004386:Duodenum / Q000378:metabolism*; D004843:Epistasis, Genetic; D005215:Fasting / Q000097:blood; D015390:Gastric Bypass; D015870:Gene Expression; D008297:Male; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D062085:RNA, Long Noncoding / Q000378:metabolism*; D011897:Random Allocation; D015854:Up-Regulation / Q000502:physiology
chemical_list: D001786:Blood Glucose; D062085:RNA, Long Noncoding
keywords: Bariatric surgery; Duodenal-jejunal bypass (DJB); Long noncoding RNAs (lncRNAs); Microarray; Type 2 diabetes (T2D)