Fructose consumption impairs serotonergic signaling in the murine enteric nervous system.
The intake of free fructose has increased substantially since the development of high-fructose corn syrup. This has not only been associated with metabolic disorders but recent evidence also indicates that chronic fructose consumption can affect neuronal and cognitive function. In this study we investigated the effects of fructose consumption on serotonergic signaling and neuronal activity in the mouse submucous plexus. Male mice were put on a control or fructose (23% solution) diet for 6 weeks or were assigned to a recovery group that received normal water (2 weeks) after 4 weeks of fructose. At the end of the diet, gene expressions and enteric neuronal activity, after depolarization with high K(+) and 5-HT, were measured using Ca(2+) imaging and RT-qPCR, respectively. Even in the lack of gain weight and the absence of changes in duodenal permeability, the total number of 5-HT-responding neurons and the depolarization and 5-HT-evoked Ca(2+) amplitudes were significantly lower after fructose consumption. Expression of synaptobrevin CaV 2.1 and CaV 2.2 mRNA did not differ after fructose intake; however, CaV 2.1 mRNA levels were significantly higher in the recovery animals. SERT mRNA concentration, isolated from submucosal plexus containing mucosal epithelium, was significantly decreased after fructose consumption. Chronic fructose consumption impairs serotonergic signaling in the mouse submucous plexus, prior to weight gain and detectable intestinal permeability problems.
Laboratory for Enteric NeuroScience (LENS), University of Leuven, Leuven, Belgium.|Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
K
K
Lowette
Laboratory for Enteric NeuroScience (LENS), University of Leuven, Leuven, Belgium.|Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
A-S
AS
Desmet
Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
R M
RM
Farré
Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
J
J
Tack
Laboratory for Enteric NeuroScience (LENS), University of Leuven, Leuven, Belgium.|Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
P
P
Vanden Berghe
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004032:Diet; D017615:Enteric Nervous System / Q000187:drug effects* / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage*; D051379:Mice; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013368:Submucous Plexus / Q000187:drug effects* / Q000378:metabolism
D005632:Fructose; D012701:Serotonin; D002118:Calcium
calcium imaging; enteric neuron; fructose; monosaccharide; serotonin