title: Significant obesity-associated gene expression changes occur in the stomach but not intestines in obese mice.
abstract: The gastrointestinal (GI) tract can have significant impact on the regulation of the whole-body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analysis in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, significant changes in the gene expression were observed in both obese mouse groups in the stomach (ob/ob: 959; HFD: 542). In addition, these changes were quantitatively much higher than in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes, and insulin resistance. In addition, the gene expression profiles strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity in murine models extensively used in research.
authors.affiliation: Computational Biology, Target Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Enteroendocrinology DPU, GlaxoSmithKline, Research Triangle Park, North Carolina.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Computational Biology, Target Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sanseau
authors.affiliation: Computational Biology, Target Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Freudenberg
authors.affiliation: Computational Biology, Target Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania deepak.k.rajpal@gsk.com.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Rajpal
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D005753:Gastric Mucosa / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*
keywords: Diet‐induced changes; metabolic diseases; obesity; obesity mechanisms; stomach; transcriptomics