A Western diet increases serotonin availability in rat small intestine.
Diet-induced obesity is associated with changes in gastrointestinal function and induction of a mild inflammatory state. Serotonin (5-HT) containing enterochromaffin (EC) cells within the intestine respond to nutrients and are altered by inflammation. Thus, our aim was to characterize the uptake and release of 5-HT from EC cells of the rat ileum in a physiologically relevant model of diet-induced obesity. In chow-fed (CF) and Western diet-fed (WD) rats electrochemical methods were used to measure compression evoked (peak) and steady state (SS) 5-HT levels with fluoxetine used to block the serotonin reuptake transporter (SERT). The levels of mRNA for tryptophan hydroxylase 1 (TPH1) and SERT were determined by quantitative PCR, while EC cell numbers were determined immunohistochemically. In WD rats, the levels of 5-HT were significantly increased (SS: 19.2 ± 3.7 μm; peak: 73.5 ± 14.1 μm) compared with CF rats (SS: 12.3 ± 1.8 μm; peak: 32.2 ± 7.2 μm), while SERT-dependent uptake of 5-HT was reduced (peak WD: 108% of control versus peak CF: 212% control). In WD rats, there was a significant increase in TPH1 mRNA, a decrease in SERT mRNA and protein, and an increase in EC cells. In conclusion, our data show that foods typical of a Western diet are associated with an increased 5-HT availability in the rat ileum. Increased 5-HT availability is driven by the up-regulation of 5-HT synthesis genes, decreased re-uptake of 5-HT, and increased numbers and/or 5-HT content of EC cells which are likely to cause altered intestinal motility and sensation in vivo.
Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney NSW 2052, Australia. dr.p.bertrand@gmail.com
R L
RL
Bertrand
S
S
Senadheera
I
I
Markus
L
L
Liu
L
L
Howitt
H
H
Chen
T V
TV
Murphy
S L
SL
Sandow
P P
PP
Bertrand
D000818:Animals; D001786:Blood Glucose; D004032:Diet; D004195:Disease Models, Animal; D004563:Electrochemistry / Q000379:methods; D005786:Gene Expression Regulation; D007082:Ileum / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C482440:Sert1 protein, rat; D012701:Serotonin; D014365:Tryptophan Hydroxylase; C504570:tph1 protein, rat