Cell Mol Gastroenterol Hepatol
March 2025
Background & Aims: Circadian disturbances result in adverse health effects, including gastrointestinal symptoms. We investigated which physiological pathways in jejunal mucosa were disrupted during chronic jetlag and prevented during time-restricted feeding (TRF). Enteroids from Bmal1 and Bmal1 mice were used to replicate the processes that were affected by chronic jetlag and rescued by TRF.
View Article and Find Full Text PDFStem cells are a keystone of intestinal homeostasis, but their function could be shifted during energy imbalance or by crosstalk with microbial metabolites in the stem cell niche. This study reports the effect of obesity and microbiota-derived short-chain fatty acids (SCFAs) on intestinal stem cell (ISC) fate in human crypt-derived intestinal organoids (enteroids). ISC fate decision was impaired in obesity, resulting in smaller enteroids with less outward protruding crypts.
View Article and Find Full Text PDFThe direct infusion of bitter solutions in the gastrointestinal tract can reduce the secretion of orexigenic hormones and influence appetite and food intake. We aimed to explore whether oral ingestion of the bitter tastant hydroxychloroquine sulfate can exert similar effects. Ten lean adult women were included in this double-blind, randomized, two-visit, crossover study.
View Article and Find Full Text PDFBackground: Secondary bile acids entrain peripheral circadian clocks and inhibit colonic motility via the bile acid receptor GPBAR1. We aimed to investigate whether chronodisruption affected the rhythm in serum bile acid levels and whether this was associated with alterations in clock gene and Gpbar1 mRNA expression in the colonic smooth muscle layer. We hypothesized that this in turn may affect the rhythm in the inhibitory effect of secondary bile acids on colonic contractility.
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View Article and Find Full Text PDFWe used time-restricted feeding (TRF) to investigate whether microbial metabolites and the hunger hormone ghrelin can become the dominant entraining factor during chronic jetlag to prevent disruption of the master and peripheral clocks, in order to promote health. Therefore, hypothalamic clock gene and mRNA expression were measured in mice that were either chronically jetlagged and fed ad libitum, jetlagged and fed a TRF diet, or not jetlagged and fed a TRF diet. Fecal short-chain fatty acid (SCFA) concentrations, plasma ghrelin and corticosterone levels, and colonic clock gene mRNA expression were measured.
View Article and Find Full Text PDFBitter taste receptors (taste 2 receptors, TAS2Rs) serve as warning sensors in the lingual system against the ingestion of potentially poisonous food. Here, we investigated the functional role of TAS2Rs in the human gut and focused on their potential to trigger an additional host defense pathway in the intestine. Human jejunal crypts, especially those from individuals with obesity, responded to bitter agonists by inducing the release of antimicrobial peptides (α-defensin 5 and regenerating islet-derived protein 3 α [REG3A]) but also regulated the expression of other innate immune factors (mucins, chemokines) that affected E.
View Article and Find Full Text PDFAim: Chronodisruption desynchronizes peripheral clocks and leads to metabolic diseases. Feeding cues are important synchronizers of peripheral clocks and influence rhythmic oscillations in intestinal microbiota and their metabolites. We investigated whether chronic jetlag, mimicking frequent time zone travelling, affected the diurnal fluctuations in faecal short-chain fatty acid (SCFA) levels, that feed back to the gut clock to regulate rhythmicity in gut function.
View Article and Find Full Text PDFChemosensory signaling in organs such as the mouth and gut contributes to the mechanisms that control metabolism. We investigated the chemosensory pathways that regulate secretion of the hunger hormone ghrelin in response to neurotransmitters, bitter and sweet tastants at the cellular level in the human gut mucosa, and the disturbances in this regulatory pathway induced by obesity. Obesity impaired ghrelin protein production and adrenalin-induced ghrelin secretion in fundic cells, which was counterbalanced by somatostatin.
View Article and Find Full Text PDFAim: The microbiota shows diurnal oscillations that are synchronized by the host's circadian clock and feeding rhythms. Short-chain fatty acids (SCFAs) produced by the microbiota are possible synchronizers of peripheral circadian clocks. We aimed to investigate whether faecal SCFAs show a diurnal rhythm that regulates the rhythm of SCFA receptor expression (FFAR2/3, OLFR78, HCAR2) and SCFA-induced colonic contractility.
View Article and Find Full Text PDFScope: The satiation properties of proteins involve effects on gut peptide release and gastrointestinal motility which may be altered during obesity. This study compares the in vitro response and role of amino acid (AA) taste receptors (TASR) in the effect of AAs and a casein hydrolysate on ghrelin release and smooth muscle (SM) contractions in the proximal gut of lean and obese patients.
Methods And Results: Basal ghrelin release, measured from mucosal segments, is maximal in the fundus and decreased distally.
Bitter taste receptors (TAS2Rs) are present in extra-oral tissues, including gut endocrine cells. This study explored the presence and mechanism of action of TAS2R agonists on gut smooth muscle in vitro and investigated functional effects of intra-gastric administration of TAS2R agonists on gastric motility and satiation. TAS2Rs and taste signalling elements were expressed in smooth muscle tissue along the mouse gut and in human gastric smooth muscle cells (hGSMC).
View Article and Find Full Text PDFBackground: In our 24-hour society, an increasing number of people are required to be awake and active at night. As a result, the circadian rhythm of feeding is seriously compromised. To mimic this, we subjected mice to restricted feeding (RF), a paradigm in which food availability is limited to short and unusual times of day.
View Article and Find Full Text PDFObestatin has recently been discovered in the rat stomach. As for ghrelin, the 23-amino acid obestatin is also derived from post-translational processing of the prepro-ghrelin gene but seems to have opposite effects on feed intake. In avian species, ghrelin is mainly present in the proventriculus and decreases feed intake, as opposed to its orexigenic properties in mammals.
View Article and Find Full Text PDFGhrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (i) ghrelin release via α-gustducin and (ii) food intake and gastric emptying via the release of ghrelin.
View Article and Find Full Text PDFBackground And Purpose: The underlying mechanisms of gastric dysfunction during or after an episode of intestinal inflammation are poorly understood. This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum.
Experimental Approach: Myeloperoxidase (MPO) activity, NF-kappaB activity and motilin receptor density were determined in the antrum of rabbits 5 days after the induction of 2,4,6-trinitrobenzenesulphonic acid colitis.
Background & Aims: Ghrelin is an orexigenic peptide with gastroprokinetic effects. Mice with streptozotocin (STZ)-induced diabetes exhibit hyperphagia, altered gastric emptying, and increased plasma ghrelin levels. We investigated the causative role of ghrelin herein by comparing changes in ghrelin receptor knockout (growth hormone secretagogue receptor [GHS-R](-/-)) and wild-type (GHS-R(+/+)) mice with STZ-induced diabetes.
View Article and Find Full Text PDFGhrelin is an orexigenic peptide present in the stomach with gastroprokinetic properties. Previous in vivo studies have shown that the ghrelin receptor antagonist, D-Lys(3)-GHRP-6, reduced food intake and delayed gastric emptying in rodents but these effects are at variance with the normal phenotype of the ghrelin knockout mice. To verify the specificity of the effects observed with D-Lys(3)-GHRP-6 this study aimed to investigate the pharmacology of D-Lys(3)-GHRP-6 in vitro.
View Article and Find Full Text PDFUnlabelled: Ghrelin and motilin form a new family of structurally related peptides. We compared the gastroprokinetic effects of ghrelin, the ghrelin receptor agonist, growth hormone releasing peptide 6 (GHRP-6), and motilin in rats in vivo and in vitro.
Methods: Ghrelin, GHRP-6 or motilin (10-150 microg/kg) were injected i.
Tachyphylaxis may have contributed to the failure of the motilide ABT-229 [N-ethyl, N-methyl 4'' deoxy erythromycin (EM)-B enolether] in clinical trials. We compared the desensitizing potency of structurally related motilides [EM-A, EM-A enolether (ME4), N-ethyl, N-methyl EM-A (ME36), EM-B enolether (ME67), N-ethyl, N-methyl EM-A enolether (EM523), ABT-229 and 4'' deoxy EM-A enolether (KOS1326)] in a Chinese hamster ovary (CHO)-K1 cell line expressing the human motilin receptor (MTLR) and in rabbit duodenal segments. CHO-MTLR cells were preincubated with motilides prior to stimulation with motilin.
View Article and Find Full Text PDFTreatment with the anti-inflammatory cytokine, interleukin-11 (IL-11), in rabbits with TNBS-colitis reduces tissue damage but does not normalize body weight loss despite an increase in plasma levels of motilin, known to stimulate food intake. We investigated whether IL-11 could increase plasma levels of the anorectic peptide, leptin in non-inflamed and inflamed rabbits. In addition, the effect of IL-11 and leptin on motilin mRNA expression in the T84 cell line was tested.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
March 2003
Aim: Electrical stimulation of colonic muscles elicits a response during the stimulation period, and a transient excitation after the stimulus. Post-stimulus or "rebound" excitation has been linked to pathways involving inhibitory neurotransmitters, prostaglandins and substance P but the mechanism is incompletely understood. Because rabbit colitis is characterized by a loss of inhibitory neurotransmission we hypothesized it might affect the rebound response.
View Article and Find Full Text PDFThe structural relationship between the motilin and the growth hormone secretagogue receptor (GHS-R), and between their respective ligands, motilin and ghrelin, prompted us to investigate whether ghrelin and the GHS-R agonist growth hormone-releasing peptide-6 (GHRP-6), could interact with the motilin receptor. The interaction was evaluated in the rabbit gastric antrum with binding studies on membrane preparations and with contraction studies on muscle strips in the presence of selective antagonists under conditions of electrical field stimulation (EFS) or not. Binding studies indicated that the affinity (pK(d)) for the motilin receptor was in the order of ghrelin (4.
View Article and Find Full Text PDF1. Inflammation may affect subpopulations of neurons of the myenteric plexus. 2.
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