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Diet‐induced Weight Loss Changes in Gene Regulatory Networks in the Rectum: Network Analysis as a Compliment to Traditional Gene Expression Analysis
Author(s) -
Vargas Ashley,
Quackenbush John,
Glass Kimberly
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.275.5
Subject(s) - gene expression , transcription factor , weight loss , biology , gene , gene regulatory network , colorectal cancer , regulation of gene expression , bioinformatics , genetics , endocrinology , cancer , obesity
Objective To determine if there are different transcription factor‐gene relationships in rectal mucosa tissue after ~10% body weight loss. Methods 10 obese women underwent clinically supervised weight loss via a very low calorie diet. Rectal mucosal biopsies were obtained before and after the ~ 46.5 day intervention, and mRNA expression was measured. An earlier study used a traditional analysis approach (Gene Set Enrichment Analysis; GSEA) to examine changes in expression. However, we hypothesize that building a network that includes known transcription factors‐gene relationships provides more detail on how regulatory pathways are changed. A network of transcription factor‐gene interactions was constructed for baseline and for end‐of‐study samples using Passing Attributes between Networks for Data Assimilation (PANDA). The baseline network was then compared to the end‐of‐study network to look for regulatory and pathways changes. Results The transcription factors NFκB1, INSM1 and MAX are all changing their targets between baseline and end‐of‐study samples. Further, changes in glucose transport from baseline to end‐of‐study were observed. Conclusions Complementing traditional GSEA analyses, this network approach identified changes in glucose transport. These changes are supported by circulating biomarkers of glucose tolerance and suggest that NFκB1, INSM1 and MAX are the key mediators of the effect of weight loss in rectal mucosa.