scholarly journals Circadian Rhythms and the Gastrointestinal Tract: Relationship to Metabolism and Gut Hormones

Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Alexandre Martchenko ◽  
Sarah E Martchenko ◽  
Andrew D Biancolin ◽  
Patricia L Brubaker
Keyword(s):  
Circadian Rhythms ◽  
Metabolic Control ◽  
Metabolic Diseases ◽  
Environmental Changes ◽  
Significant Risk ◽  
Gut Hormones ◽  
Circadian System ◽  
Metabolic Homeostasis ◽  
Gi Tract ◽  
Gut Hormone

Abstract Circadian rhythms are 24-hour biological rhythms within organisms that have developed over evolutionary time due to predefined environmental changes, mainly the light-dark cycle. Interestingly, metabolic tissues, which are largely responsible for establishing diurnal metabolic homeostasis, have been found to express cell-autonomous clocks that are entrained by food intake. Disruption of the circadian system, as seen in individuals who conduct shift work, confers significant risk for the development of metabolic diseases such as type 2 diabetes and obesity. The gastrointestinal (GI) tract is the first point of contact for ingested nutrients and is thus an essential organ system for metabolic control. This review will focus on the circadian function of the GI tract with a particular emphasis on its role in metabolism through regulation of gut hormone release. First, the circadian molecular clock as well as the organization of the mammalian circadian system is introduced. Next, a brief overview of the structure of the gut as well as the circadian regulation of key functions important in establishing metabolic homeostasis is discussed. Particularly, the focus of the review is centered around secretion of gut hormones; however, other functions of the gut such as barrier integrity and intestinal immunity, as well as digestion and absorption, all of which have relevance to metabolic control will be considered. Finally, we provide insight into the effects of circadian disruption on GI function and discuss chronotherapeutic intervention strategies for mitigating associated metabolic dysfunction.

scholarly journals The gut hormone Allatostatin C regulates food intake and metabolic homeostasis under nutrient stress

2020 ◽  
Author(s):  
Olga Kubrak ◽  
Line Jensen ◽  
Nadja Ahrentløv ◽  
Takashi Koyama ◽  
Alina Malita ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Somatostatin Receptors ◽  
Gut Hormones ◽  
Peptide Hormone ◽  
Nutrient Stress ◽  
Metabolic Homeostasis ◽  
Adipokinetic Hormone ◽  
Energy Mobilization ◽  
Gut Hormone

AbstractThe intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the specific gut hormones that communicate energy availability to target organs to induce appropriate metabolic and behavioral responses are poorly defined. Here we show that the enteroendocrine cells (EECs) of the Drosophila gut sense nutrient stress via the intracellular TOR pathway, and in response secrete the peptide hormone allatostatin C (AstC). Gut-derived AstC induces secretion of glucagon-like adipokinetic hormone (AKH) via its receptor AstC-R2, a homolog of mammalian somatostatin receptors, to coordinate food intake and energy mobilization. Loss of gut AstC or its receptor in the AKH-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders.

scholarly journals Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
F. J. Valenzuela ◽  
J. Vera ◽  
C. Venegas ◽  
S. Muñoz ◽  
S. Oyarce ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Metabolic Diseases ◽  
Environmental Changes ◽  
Clock Genes ◽  
Genetic Interaction ◽  
Circadian System ◽  
Feeding Time ◽  
Genetic Components ◽  
Molecular Components ◽  
Risk Of Cancer

The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genesClock,Bmal1,Per1–3,andCry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined.

scholarly journals Circadian rhythms in mitochondrial respiration

2018 ◽  
Vol 60 (3) ◽  
pp. R115-R130 ◽  
Author(s):  
Paul de Goede ◽  
Jakob Wefers ◽  
Eline Constance Brombacher ◽  
Patrick Schrauwen ◽  
Andries Kalsbeek
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Mitochondrial Respiration ◽  
Metabolic Diseases ◽  
Environmental Changes ◽  
Morphological Changes ◽  
Active Phase ◽  
Whole Body ◽  
Mitochondrial Morphology ◽  
Diurnal Changes

Many physiological processes are regulated with a 24-h periodicity to anticipate the environmental changes of daytime to nighttime and vice versa. These 24-h regulations, commonly termed circadian rhythms, among others control the sleep–wake cycle, locomotor activity and preparation for food availability during the active phase (daytime for humans and nighttime for nocturnal animals). Disturbing circadian rhythms at the organ or whole-body level by social jetlag or shift work, increases the risk to develop chronic metabolic diseases such as type 2 diabetes mellitus. The molecular basis of this risk is a topic of increasing interest. Mitochondria are essential organelles that produce the majority of energy in eukaryotes by converting lipids and carbohydrates into ATP through oxidative phosphorylation. To adapt to the ever-changing environment, mitochondria are highly dynamic in form and function and a loss of this flexibility is linked to metabolic diseases. Interestingly, recent studies have indicated that changes in mitochondrial morphology (i.e., fusion and fission) as well as generation of new mitochondria are dependent on a viable circadian clock. In addition, fission and fusion processes display diurnal changes that are aligned to the light/darkness cycle. Besides morphological changes, mitochondrial respiration also displays diurnal changes. Disturbing the molecular clock in animal models leads to abrogated mitochondrial rhythmicity and altered respiration. Moreover, mitochondrial-dependent production of reactive oxygen species, which plays a role in cellular signaling, has also been linked to the circadian clock. In this review, we will summarize recent advances in the study of circadian rhythms of mitochondria and how this is linked to the molecular circadian clock.

scholarly journals Gut chemosensing: implications for disease pathogenesis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2424 ◽  
Author(s):  
Christopher J. Berg ◽  
Jonathan D. Kaunitz
Keyword(s):  
Nervous System ◽  
Metabolic Diseases ◽  
Gastric Bypass Surgery ◽  
Gut Hormones ◽  
Gut Peptides ◽  
Sensory Data ◽  
Gut Hormone ◽  
Gut Mucosa ◽  
The Central Nervous System ◽  
Bile Acid Receptors

The ability of humans to sense chemical signals in ingested substances is implicit in the ability to detect the five basic tastes; sweet, sour, bitter, salty, and umami. Of these, sweet, bitter, and umami tastes are detected by lingual G-protein-coupled receptors (GPCRs). Recently, these receptors were also localized to the gut mucosa. In this review, we will emphasize recent advances in the understanding of the mechanisms and consequences of foregut luminal chemosensing, with special emphasis on cell surface GPCRs such as the sweet and proteinaceous taste receptors (TASRs), short- and long-chain fatty acid (FA) receptors, and bile acid receptors. The majority of these luminal chemosensors are expressed on enteroendocrine cells (EECs), which are specialized endocrine cells in the intestine and pancreas that release gut hormones with ligand activation. These gut hormones are responsible for a wide variety of physiologic and homeostatic mechanisms, including glycemic control, appetite stimulation and suppression, regulation of gastric emptying, and trophic effects on the intestinal epithelium. Released from the EECs, the gut peptides have paracrine, autocrine, and endocrine effects. Additionally, EECs have unique direct connections to the enteric nervous system enabling precise transmission of sensory data to and communication with the central nervous system. We will also describe how gut sensors are implicated in gut hormone release, followed by examples of how altered gut chemosensing has been implicated in pathological conditions such as metabolic diseases including diabetes and obesity, functional dyspepsia, helminthic infections, colitis, gastric bypass surgery, and gastric inflammation and cancer.

scholarly journals Phosphorylation and Circadian Molecular Timing

2020 ◽  
Vol 11 ◽  
Author(s):  
Andrea Brenna ◽  
Urs Albrecht
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Environmental Changes ◽  
Circadian System ◽  
Post Translational Modifications ◽  
Physiological Processes ◽  
Clock Proteins ◽  
Protein Components ◽  
Response To Environmental Change ◽  
External Stimuli

Endogenous circadian rhythms are biological processes generated by an internal body clock. They are self-sustaining, and they govern biochemical and physiological processes. However, circadian rhythms are influenced by many external stimuli to reprogram the phase in response to environmental change. Through their adaptability to environmental changes, they synchronize physiological responses to environmental challenges that occur within a sidereal day. The precision of this circadian system is assured by many post-translational modifications (PTMs) that occur on the protein components of the circadian clock mechanism. The most ancient example of circadian rhythmicity driven by phosphorylation of clock proteins was observed in cyanobacteria. The influence of phosphorylation on the circadian system is observed through different kingdoms, from plants to humans. Here, we discuss how phosphorylation modulates the mammalian circadian clock, and we give a detailed overview of the most critical discoveries in the field.

scholarly journals The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress

2021 ◽  
Author(s):  
Olga Kubrak ◽  
Line Jensen ◽  
Nadja Ahrentloev ◽  
Takashi Koyama ◽  
Alina Malita ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Somatostatin Receptors ◽  
Gut Hormones ◽  
Peptide Hormone ◽  
Nutrient Stress ◽  
Metabolic Homeostasis ◽  
Adipokinetic Hormone ◽  
Energy Mobilization ◽  
Gut Hormone

Abstract The intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the specific gut hormones that communicate energy availability to target organs to induce appropriate metabolic and behavioral responses are poorly defined. Here we show that the enteroendocrine cells (EECs) of the Drosophila gut sense nutrient stress via the intracellular TOR pathway, and in response secrete the peptide hormone allatostatin C (AstC), a Drosophila Somatostatin homolog. Gut-derived AstC induces secretion of glucagon-like adipokinetic hormone (AKH) via its receptor AstC-R2, a homolog of mammalian somatostatin receptors, to coordinate food intake and energy mobilization. Loss of gut AstC or its receptor in the AKH-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders.

Dissociable hormonal responses to symptoms and stress in anorexia and bulimia nervosa

2019 ◽  
Author(s):  
Margaret L Westwater ◽  
Flavia Mancini ◽  
Jane Shapleske ◽  
Jaco Serfontein ◽  
Monique Ernst ◽  
...  
Keyword(s):  
Bulimia Nervosa ◽  
Acute Stress ◽  
Gut Hormones ◽  
Metabolic Dysfunction ◽  
Cortisol Reactivity ◽  
Psychological States ◽  
Study Session ◽  
Gut Hormone ◽  
Ad Libitum ◽  
Acyl Ghrelin

Background: Anorexia nervosa (AN) and bulimia nervosa (BN) are complex psychiatric conditions, in which both psychological and metabolic factors have been implicated. Critically, the experience of stress can precipitate loss-of-control eating in both conditions, suggesting an interplay between mental state and metabolic signaling. However, associations between psychological states, symptoms and metabolic processes in AN and BN have not been examined. Methods: Eighty-five women (n=22 AN binge/purge subtype, n=33 BN, n=30 controls) underwent remote salivary cortisol sampling and a two-day, inpatient study session to examine the effect of stress on cortisol, gut hormones (acyl-ghrelin, PYY, GLP-1) and food consumption. Participants were randomized to either an acute stress induction or control task on each day, and plasma hormones were serially measured before a naturalistic, ad libitum meal.Results: Cortisol awakening response (CAR) was augmented in AN but not BN relative to controls, with body mass index explaining the most variance in CAR (36%). Acute stress increased acyl-ghrelin and PYY in AN compared to controls; however, stress did not alter gut hormone profiles in BN. Instead, a group-by-stress interaction showed nominally reduced cortisol reactivity in BN, but not AN, compared to controls. Ad libitum consumption was lower in both patient groups and unaffected by stress.Conclusions: Findings extend previous reports of metabolic dysfunction in binge-eating disorders, identifying unique associations across disorders and under stress. Moreover, we observed disrupted homeostatic signaling in AN following psychological stress, which may explain, in part, the maintenance of dysregulated eating in this serious illness.

scholarly journals Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 174
Author(s):  
Anne Christin Meyer-Gerspach ◽  
Jürgen Drewe ◽  
Wout Verbeure ◽  
Carel W. le Roux ◽  
Ludmilla Dellatorre-Teixeira ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gastric Emptying ◽  
Blood Lipids ◽  
Tap Water ◽  
Hormone Secretion ◽  
Gastrointestinal Symptoms ◽  
Gut Hormones ◽  
Double Blind ◽  
Gut Hormone ◽  
Dose Dependent

Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.

scholarly journals The Emerging Role of Polyphenols in the Management of Type 2 Diabetes

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 703
Author(s):  
Yao Wang ◽  
Hana Alkhalidy ◽  
Dongmin Liu
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Homeostasis ◽  
Gut Hormones ◽  
Nutritional Regulation ◽  
Gi Tract ◽  
Cell Dysfunction ◽  
Glucagon Like Peptide 1 ◽  
Metabolic Action

Type 2 diabetes (T2D) is a fast-increasing health problem globally, and it results from insulin resistance and pancreatic β-cell dysfunction. The gastrointestinal (GI) tract is recognized as one of the major regulatory organs of glucose homeostasis that involves multiple gut hormones and microbiota. Notably, the incretin hormone glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells plays a pivotal role in maintaining glucose homeostasis via eliciting pleiotropic effects, which are largely mediated via its receptor. Thus, targeting the GLP-1 signaling system is a highly attractive therapeutic strategy to treatment T2D. Polyphenols, the secondary metabolites from plants, have drawn considerable attention because of their numerous health benefits, including potential anti-diabetic effects. Although the major targets and locations for the polyphenolic compounds to exert the anti-diabetic action are still unclear, the first organ that is exposed to these compounds is the GI tract in which polyphenols could modulate enzymes and hormones. Indeed, emerging evidence has shown that polyphenols can stimulate GLP-1 secretion, indicating that these natural compounds might exert metabolic action at least partially mediated by GLP-1. This review provides an overview of nutritional regulation of GLP-1 secretion and summarizes recent studies on the roles of polyphenols in GLP-1 secretion and degradation as it relates to metabolic homeostasis. In addition, the effects of polyphenols on microbiota and microbial metabolites that could indirectly modulate GLP-1 secretion are also discussed.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

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