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Comprehensive analysis of localization of 78 solute carrier genes throughout the subsections of the rat 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, Functional Pharmacology.
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2011 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 411, no 4, 702-707 p.Article in journal (Refereed) Published
Abstract [en]

Solute carriers (SLCs), the second largest super-family of membrane proteins in the human genome, transport amino acids, sugars, fatty acids, inorganic ions, essential metals and drugs over membranes. To date no study has provided a comprehensive analysis of SLC localization along the entire GI tract. The aim of the present study was to provide a comprehensive, segment-specific description of the localization of SLC genes along the rat Cl tract by employing bioinformatics and molecular biology methods. The Unigene database was screened for rat SLC entries in the intestinal tissue. Using qPCR we measured expression of the annotated genes in the Cl tract divided into the following segments: the esophagus, the corpus and the antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum. Our Unigene-derived gene pool was expanded with data from in-house tissue panels and a literature search. We found 44 out of 78 (56%) of gut SLC transcripts to be expressed in all Cl tract segments, whereas the majority of remaining SLCs were detected in more than five segments. SLCs are predominantly expressed in gut regions with absorptive functions although expression was also found in segments unrelated to absorption. The proximal jejunum had the highest number of differentially expressed SLCs. In conclusion, SLCs are a crucial molecular component of the Cl tract, with many of them expressed along the entire GI tract. This work presents the first overall road map of localization of transporter genes in the Cl tract.

Place, publisher, year, edition, pages
2011. Vol. 411, no 4, 702-707 p.
Keyword [en]
Solute carriers, GI tract, RT-qPCR, Anatomical localization, Twelve subsections
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-159051DOI: 10.1016/j.bbrc.2011.07.005ISI: 000294317300009OAI: oai:DiVA.org:uu-159051DiVA: diva2:442866
Available from: 2011-09-22 Created: 2011-09-21 Last updated: 2017-12-08Bibliographically 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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Supervisors
Available from: 2013-03-27 Created: 2013-03-05 Last updated: 2013-04-02Bibliographically approved

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