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Sex Differences in Jejunal Mucosal 5‐HT (serotonin) Availability in a Diet‐Induced Obesity (DIO) Mouse Model
Author(s) -
France Marion,
Galligan James,
Swain Greg
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.848.5
Subject(s) - endocrinology , medicine , jejunum , serotonin transporter , serotonin , extracellular , enterochromaffin cell , serotonin plasma membrane transport proteins , neurotransmitter , biology , fluoxetine , reuptake , ileum , 5 ht receptor , chemistry , receptor , biochemistry , central nervous system
Background Increased gut transit results from greater mucosal 5‐HT availability that is reliant on 5‐HT uptake by the serotonin transporter (SERT) following release from enterochromaffin (EC) cells. We determined if jejunal 5‐HT availability in high fat (HF) obese mice of both sexes is altered compared to control mice. Methods: 5‐HT uptake was assessed using SERT and dopamine transporter (DAT) inhibitors, fluoxetine (1 μM) and GBR 12909 (0.1 μM) in amperometric experiments, respectively. HPLC measured mucosal whole tissue 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA) and extracellular 5‐HT near the mucosa. Mucosal SERT protein and mRNA were measured using Western blotting and RT‐PCR, respectively. 5‐HT positive cells were identified using immunohistochemistry. ELISA measured plasma estradiol and progesterone. Results: 5‐HT uptake was insensitive to fluoxetine and sensitive to GBR 12909 in male HF jejunum vs. controls. SERT protein levels, whole tissue 5‐HIAA and extracellular 5‐HT were similar in male HF and controls. Male and female whole tissue 5‐HT levels and EC cell counts were similar in HF and controls. Female HF jejunum was sensitive to fluoxetine and had greater SERT protein levels independent of mRNA vs. controls. Extracellular 5‐HT levels were decreased in HF vs. controls. Plasma estradiol and progesterone levels were similar in HF and controls. Conclusions Sex differences in mucosal 5‐HT availability in DIO exist. Impaired SERT function in HF male jejunum can increase 5‐HT availability and may be compensated for by DAT. In HF female jejunum, greater SERT protein can decrease 5‐HT availability.