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Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
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2012 (English)In: BMC gastroenterology, ISSN 1471-230X, Vol. 12, 134- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments.

METHODS: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum.

RESULTS: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.

CONCLUSIONS: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions.

Place, publisher, year, edition, pages
2012. Vol. 12, 134- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-190104DOI: 10.1186/1471-230X-12-134ISI: 000312734600001PubMedID: 23009096OAI: oai:DiVA.org:uu-190104DiVA: diva2:583003
Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2013-04-02Bibliographically approved
In thesis
1. Intestinal Gene Expression Profiling and Fatty Acid Responses to a High-fat Diet
Open this publication in new window or tab >>Intestinal Gene Expression Profiling and Fatty Acid Responses to a High-fat Diet
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The gastrointestinal tract (GIT) regulates nutrient uptake, secretes hormones and has a crucial gut flora and enteric nervous system. Of relevance for these functions are the G protein-coupled receptors (GPCRs) and the solute carriers (SLCs). The Adhesion GPCR subfamily is known to mediate neural development and immune system functioning, whereas SLCs transport e.g. amino acids, fatty acids (FAs) and drugs over membranes. We aimed to comprehensively characterize Adhesion GPCR and SLC gene expression along the rat GIT. Using qPCR we measured expression of 78 SLCs as well as all 30 Adhesion GPCRs in a twelve-segment GIT model. 21 of the Adhesion GPCRs had a widespread (≥5 segments) or ubiquitous (≥11 segments) expression. Restricted expression patterns were characteristic for most group VII members. Of the SLCs, we found the majority (56 %) of these transcripts to be expressed in all GIT segments. SLCs were predominantly found in the absorption-responsible gut regions. Both Adhesion GPCRs and SLCs were widely expressed in the rat GIT, suggesting important roles. The distribution of Adhesion GPCRs defines them as a potential pharmacological target.

FAs constitute an important energy source and have been implicated in the worldwide obesity increase. FAs and their ratios – indices for activities of e.g. the desaturase enzymes SCD-1 (SCD-16, 16:1n-7/16:0), D6D (18:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6) – have been associated with e.g. overall mortality and BMI. We examined whether differences in FAs and their indices in five lipid fractions contributed to obesity susceptibility in rats fed a high fat diet (HFD), and the associations of desaturase indices between lipid fractions in animals on different diets. We found that on a HFD, obesity-prone (OP) rats had a higher SCD-16 index and a lower linoleic acid (LA) proportions in subcutaneous adipose tissue (SAT) than obesity-resistant rats. Desaturase indices were significantly correlated between many of the lipid fractions. The higher SCD-16 may indicate higher SCD-1 activity in SAT in OP rats, and combined with lower LA proportions may provide novel insights into HFD-induced obesity. The associations between desaturase indices show that plasma measurements can serve as proxies for some lipid fractions, but the correlations seem to be affected by diet and weight gain.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 98 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 872
Keyword
Adhesion GPCR, delta-5 desaturase, delta-6 desaturase, desaturase index, Diet-induced obesity, estimated desaturase activity, fatty acid composition, gas chromatography, gastrointestinal tract, G-protein coupled receptor, high-fat diet, intestine, linoleic acid, liver, mRNA expression, palmitoleic acid, plasma, phospholipids, proximodistal, RT-qPCR, solute carrier, SCD-1, SCD-16, SCD-18, stearoyl-CoA desaturase, subcutaneous adipose tissue, subsection, triacylglycerols.
National Category
Nutrition and Dietetics Cell and Molecular Biology Medical Genetics
Research subject
Medical Genetics; Nutrition; Nutrition
Identifiers
urn:nbn:se:uu:diva-196207 (URN)978-91-554-8612-9 (ISBN)
Public defence
2013-04-18, B22, Biomedicinskt centrum, Husargatan 3, UPPSALA, 13:15 (English)
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Available from: 2013-03-27 Created: 2013-03-05 Last updated: 2013-04-02Bibliographically approved

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