title: Serotonin availability in rat colon is reduced during a Western diet model of obesity.
abstract: Constipation and slowed transit are associated with diet-induced obesity, although the mechanisms by which this occurs are unclear. Enterochromaffin (EC) cells within the intestinal epithelium respond to mechanical stimulation with the release of serotonin [5-hydroxytryptamine (5-HT)], which promotes transit. Thus our aim was to characterize 5-HT availability in the rat colon of a physiologically relevant model of diet-induced obesity. EC cell numbers were determined immunohistochemically in chow-fed (CF) and Western diet-fed (WD) rats, while electrochemical methods were used to measure mechanically evoked (peak) and steady-state (SS) 5-HT levels. Fluoxetine was used to block the 5-HT reuptake transporter (SERT), and the levels of mRNA for tryptophan hydroxylase 1 and SERT were determined by quantitative PCR, and SERT protein was determined by Western blot. In WD rats, there was a significant decrease in the total number of EC cells per crypt (0.86 ± 0.06 and 0.71 ± 0.05 in CF and WD, respectively), which was supported by a reduction in the levels of 5-HT in WD rats (2.9 ± 1.0 and 10.5 ± 2.6 μM at SS and peak, respectively) compared with CF rats (7.3 ± 0.4 and 18.4 ± 3.4 μM at SS and peak, respectively). SERT-dependent uptake of 5-HT was unchanged, which was supported by a lack of change in SERT protein levels. In WD rats, there was no change in tryptophan hydroxylase 1 mRNA but an increase in SERT mRNA. In conclusion, our data show that foods typical of a WD are associated with decreased 5-HT availability in rat colon. Decreased 5-HT availability is driven primarily by a reduction in the numbers and/or 5-HT content of EC cells, which are likely to be associated with decreased intestinal motility in vivo.
authors.affiliation: Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. dr.p.bertrand@gmail.com
authors.forename: R L
authors.initials: RL
authors.lastname: Bertrand
authors.forename: S
authors.initials: S
authors.lastname: Senadheera
authors.forename: A
authors.initials: A
authors.lastname: Tanoto
authors.forename: K L
authors.initials: KL
authors.lastname: Tan
authors.forename: L
authors.initials: L
authors.lastname: Howitt
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: T V
authors.initials: TV
authors.lastname: Murphy
authors.forename: S L
authors.initials: SL
authors.lastname: Sandow
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: P P
authors.initials: PP
authors.lastname: Bertrand
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D003248:Constipation / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; D012701:Serotonin; D014365:Tryptophan Hydroxylase