Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse Model.

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.

SCFAs switch stem cell fate through HDAC inhibition to improve barrier integrity in 3D intestinal organoids from patients with obesity.

Stem 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.

The Acute Effect of Hydroxychloroquine Sulfate on Hunger, the Plasma Concentration of Orexigenic Peptides and Hedonic Food Intake: A Pilot Study.

The 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.

Time-restricted eating for chronodisruption-related chronic diseases.

The circadian timing system enables organisms to adapt their physiology and behavior to the cyclic environmental changes including light-dark cycle or food availability. Misalignment between the endogenous circadian rhythms and external cues is known as chronodisruption and is closely associated with the development of metabolic and gastrointestinal disorders, cardiovascular diseases, and cancer. Time-restricted eating (TRE, in human) is an emerging dietary approach for weight management.

Controlled light exposure and intermittent fasting as treatment strategies for metabolic syndrome and gut microbiome dysregulation in night shift workers.

The mammalian circadian clocks are entrained by environmental time cues, such as the light-dark cycle and the feeding-fasting cycle. In modern society, circadian misalignment is increasingly more common under the guise of shift work. Shift workers, accounting for roughly 20% of the workforce population, are more susceptible to metabolic disease.

Chronic jetlag reprograms gene expression in the colonic smooth muscle layer inducing diurnal rhythmicity in the effect of bile acids on colonic contractility.

Background: 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.

Reply to Erren et al. Chronodisruption: Origin, Roots, and Developments of an 18-Year-Old Concept. Comment on "Desmet et al. Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag. 2021, , 3846".

We would like to thank Erren et al. [..

Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag.

We 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.

Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity.

Bitter 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.

Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice.

Aim: 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.

The Function of Gastrointestinal Hormones in Obesity-Implications for the Regulation of Energy Intake.

The global burden of obesity and the challenges of prevention prompted researchers to investigate the mechanisms that control food intake. Food ingestion triggers several physiological responses in the digestive system, including the release of gastrointestinal hormones from enteroendocrine cells that are involved in appetite signalling. Disturbed regulation of gut hormone release may affect energy homeostasis and contribute to obesity.

The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration.

Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill." However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: ) the site of administration: intragastrically (IG) or intraduodenally (ID), ) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and ) the timing of infusion.

Circadian clocks in the digestive system.

Many molecular, physiological and behavioural processes display distinct 24-hour rhythms that are directed by the circadian system. The master clock, located in the suprachiasmatic nucleus region of the hypothalamus, is synchronized or entrained by the light-dark cycle and, in turn, synchronizes clocks present in peripheral tissues and organs. Other environmental cues, most importantly feeding time, also synchronize peripheral clocks.

Involvement of the GHSR in the developmental programming and metabolic disturbances induced by maternal undernutrition.

The mismatch between maternal undernutrition and adequate nutrition after birth increases the risk of developing metabolic diseases. We aimed to investigate whether the hyperghrelinemia during maternal undernourishment rewires the hypothalamic development of the offspring and contributes to the conversion to an obese phenotype when fed a high-fat diet (HFD). Pregnant C57BL/6 J, wild type (WT) and ghrelin receptor (GHSR) mice were assigned to either a normal nourished (NN) group, or an undernutrition (UN) (30% food restricted) group.

Ghrelin inhibits autonomic response to gastric distension in rats by acting on vagal pathway.

Ghrelin is the only orexigenic peptide currently known and a potent prokinetic by promoting gastric motility but novel insights suggest that its role extends beyond satiety regulation. Whereas ghrelin was shown to provide somatic and colonic antinociception, its impact on gastric sensitivity is unknown even though stomach is a major ghrelin secreting tissue. Autonomic response to gastric mechanosensitivity was estimated by measuring blood pressure variation as a surrogate marker in response to gastric distension (GD) before and after ghrelin (or vehicle) administration.

Extra-oral bitter taste receptors: New targets against obesity?

Taste perception on the tongue is essential to help us to identify nutritious or potential toxic food substances. Emerging evidence has demonstrated the expression and function of bitter taste receptors (TAS2Rs) in a wide range of extra-oral tissues. In particular, TAS2Rs in gastrointestinal enteroendocrine cells control the secretion of appetite regulating gut hormones and influence hunger and food intake.

Night-time feeding of Bmal1-/- mice restores SCFA rhythms and their effect on ghrelin.

The known crosstalk between short-chain fatty acids (SCFAs) and the circadian clock is tightly intertwined with feeding time. We aimed to investigate the role of the core clock gene Bmal1 and feeding time in the diurnal rhythms in plasma and caecal SCFA levels and in their effect on the release of the hunger hormone ghrelin in the stomach and colon. WT, Bmal1-/- (ad libitum fed) and night-time-restricted-fed (RF)-Bmal1-/- littermates were killed at zeitgeber time (ZT) 4 and 16.

Review: Chemosensing of nutrients and non-nutrients in the human and porcine gastrointestinal tract.

The gastrointestinal tract (GIT) is an interface between the external and internal milieus that requires continuous monitoring for nutrients or pathogens and toxic chemicals. The study of the physiological/molecular mechanisms, mediating the responses to the monitoring of the GIT contents, has been referred to as chemosensory science. While most of the progress in this area of research has been obtained in laboratory rodents and humans, significant steps forward have also been reported in pigs.

Influence of subliminal intragastric fatty acid infusion on subjective and physiological responses to positive emotion induction in healthy women: A randomized trial.

Background: Subliminal intragastric fatty acid infusion attenuates subjective and brain responses to negative emotion induction. However, the underlying gut-brain signaling mechanisms remain unclear, and it is unknown whether such effect equally applies to positive emotion.

Objective: We aimed to investigate the interaction between fatty acid-induced gut-brain signaling and subjective responses to positive emotion, and the potential mediational role of gastrointestinal (GI) hormones.

Effect of acute Δ9-tetrahydrocannabinol administration on subjective and metabolic hormone responses to food stimuli and food intake in healthy humans: a randomized, placebo-controlled study.

Background: The endocannabinoid system (ECS) is considered a key player in the neurophysiology of food reward. Animal studies suggest that the ECS stimulates the sensory perception of food, thereby increasing its incentive-motivational and/or hedonic properties and driving consumption, possibly via interactions with metabolic hormones. However, it remains unclear to what extent this can be extrapolated to humans.

Motilin: from gastric motility stimulation to hunger signalling.

After the discovery of motilin in 1972, motilin and the motilin receptor were studied intensely for their role in the control of gastrointestinal motility and as targets for treating hypomotility disorders. The genetic revolution - with the use of knockout models - sparked novel insights into the role of multiple peptides but contributed to a decline in interest in motilin, as this peptide and its receptor exist only as pseudogenes in rodents. The past 5 years have seen a major surge in interest in motilin, as a series of studies have shown its relevance in the control of hunger and regulation of food intake in humans in both health and disease.

Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut.

Chemosensory 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.

Therapeutic potential of ectopic olfactory and taste receptors.

Olfactory and taste receptors are expressed primarily in the nasal olfactory epithelium and gustatory taste bud cells, where they transmit real-time sensory signals to the brain. However, they are also expressed in multiple extra-nasal and extra-oral tissues, being implicated in diverse biological processes including sperm chemotaxis, muscle regeneration, bronchoconstriction and bronchodilatation, inflammation, appetite regulation and energy metabolism. Elucidation of the physiological roles of these ectopic receptors is revealing potential therapeutic and diagnostic applications in conditions including wounds, hair loss, asthma, obesity and cancers.