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.
Subject(s)
Colon/metabolism , Diet/adverse effects , Enterochromaffin Cells/metabolism , Obesity/metabolism , Serotonin/metabolism , Animals , Colon/cytology , Constipation/metabolism , Diet, High-Fat/adverse effects , Enterochromaffin Cells/drug effects , Fluoxetine/pharmacology , Gastrointestinal Motility/drug effects , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Serotonin Plasma Membrane Transport Proteins/metabolism , Tryptophan Hydroxylase/metabolismABSTRACT
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.
Subject(s)
Diet , Ileum/metabolism , Obesity/metabolism , Serotonin/metabolism , Animals , Blood Glucose , Disease Models, Animal , Electrochemistry/methods , Gene Expression Regulation , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Tryptophan Hydroxylase/genetics , Tryptophan Hydroxylase/metabolismABSTRACT
Isolated ventricular non-compaction (IVNC) is an idiopathic form of cardiomyopathy. Recent clinical reports have suggested that this form of cardiomyopathy is more frequently associated with complications of congestive heart failure, thromboembolism and malignant ventricular arrhythmias. Contrast enhanced cardiac magnetic resonance imaging with its excellent spatial resolution, its large field of view and its ability to demonstrate thrombus and myocardial scar is an excellent modality to non-invasively assess patients with this form of cardiomyopathy. This paper presents a case of familial isolated ventricular non-compaction. We describe the echocardiographic, X-ray angiographic and cardiac MRI findings. Cine imaging using a steady-state free precession sequence (BFFE) was performed in axial and short axis planes. Left ventricular (LV) mass was estimated both with and without the incorporation of trabeculations from a contiguous stack of short axis images. Trabecular mass was expressed as a percentage of total left ventricular mass. We compared trabecular mass: total LV mass in 10 patients with dilated cardiomyopathy. The mean percentage trabecular mass: LV mass in dilated cardiomyopathy was 11.3% (range 1.5%-19%), and this differed significantly from the trabecular mass of the noncompaction patient (two-tailed Mann-Whitney test, p = 0.028). Trabecular mass of greater than 20% of total myocardial mass may be a useful index to suggest the diagnosis of IVNC. Gadolinium was administered (0.1 mmol/kg). Qualitative analysis of first pass perfusion suggested reduced trabecular perfusion. Early imaging with an inversion recovery sequence and a fixed long inversion time did not demonstrate LV thrombus. Late imaging with the same sequence (TI = 280-300 msec) did not demonstrate myocardial fibrosis.
