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.

The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

2019 ◽  
Vol 20 (7) ◽  
pp. 750-758 ◽  
Author(s):  
Yi Wu ◽  
Hengxun He ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropeptide Y ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
Vital Role ◽  
Gut Peptides ◽  
Nonalcoholic Fatty Liver ◽  
The Central Nervous System

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

scholarly journals Gastrointestinal hormones regulating appetite

2006 ◽  
Vol 361 (1471) ◽  
pp. 1187-1209 ◽  
Author(s):  
Owais Chaudhri ◽  
Caroline Small ◽  
Steve Bloom
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Energy Balance ◽  
Food Intake ◽  
Gastrointestinal Hormones ◽  
Gut Hormones ◽  
Gut Peptides ◽  
Appetite Control ◽  
Local Effects ◽  
The Central Nervous System

The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance. Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation. Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood–brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the central nervous system. In this way, hormonal signals from the gut may be translated into the subjective sensation of satiety. Moreover, the importance of the brain–gut axis in the control of food intake is reflected in the dual role exhibited by many gut peptides as both hormones and neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons projecting both into and out of areas of the central nervous system critical to energy balance. The global increase in the incidence of obesity and the associated burden of morbidity has imparted greater urgency to understanding the processes of appetite control. Appetite regulation offers an integrated model of a brain–gut axis comprising both endocrine and neurological systems. As physiological mediators of satiety, gut hormones offer an attractive therapeutic target in the treatment of obesity.

Acquired Diseases of the Nervous System

2018 ◽  
pp. 219-243
Author(s):  
Leila Chimelli ◽  
Françoise Gray
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Brain Regions ◽  
Vitamin Deficiencies ◽  
System P ◽  
Wide Range ◽  
The Central Nervous System ◽  
Anatomic Region

This chapter describes and illustrates the different neuropathological changes observed in a wide range of systemic acquired metabolic diseases that affect the central or peripheral nervous systems: hypoxia, hypoglycemia, hyperthermia, disorders of serum electrolytes, vitamin deficiencies, and exogenous intoxications, particularly alcoholism and intoxications by drugs, methanol, and heavy metals. In the central nervous system, lesions may find expression via selective involvement of some brain regions, with simultaneous complete preservation of others. The pathogenesis of the predisposition to injury for a particular anatomic region or for some specific set of cell types (neurons mostly) varies considerably form one disease to another and is undoubtedly multifactorial. The chapter also considers central nervous system abnormalities secondary to systemic diseases, including respiratory encephalopathies, hepatic encephalopathy, multifocal necrotizing leukoencephalopathy, and paraneoplastic encephalomyelopathies.

scholarly journals The gut endocrine system as a coordinator of postprandial nutrient homoeostasis

2012 ◽  
Vol 71 (4) ◽  
pp. 456-462 ◽  
Author(s):  
Fiona M. Gribble
Keyword(s):  
Human Subjects ◽  
Gastric Bypass Surgery ◽  
Endocrine System ◽  
Gut Hormones ◽  
Enteroendocrine Cells ◽  
Apical Surface ◽  
Hormone Release ◽  
Food Ingestion ◽  
Gut Hormone

Hormones from the gastrointestinal (GI) tract are released following food ingestion and trigger a range of physiological responses including the coordination of appetite and glucose homoeostasis. The aim of this review is to discuss the pathways by which food ingestion triggers secretion of cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) and the altered patterns of gut hormone release observed following gastric bypass surgery. Our understanding of how ingested nutrients trigger secretion of these gut hormones has increased dramatically, as a result of physiological studies in human subjects and animal models andin vitrostudies on cell lines and primary intestinal cultures. Specialised enteroendocrine cells located within the gut epithelium are capable of directly detecting a range of nutrient stimuli through a range of receptors and transporters. It is concluded that the arrival of nutrients at the apical surface of enteroendocrine cells is a major stimulus for gut hormone release, thereby coupling these endocrine signals to the arrival of absorbed nutrients in the bloodstream.

Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging

2004 ◽  
Vol 287 (5) ◽  
pp. H1895-H1905 ◽  
Author(s):  
Douglas R. Seals ◽  
Frank A. Dinenno
Keyword(s):  
Nervous System ◽  
Metabolic Diseases ◽  
Primary Response ◽  
Adrenergic Stimulation ◽  
Peripheral Tissues ◽  
Arterial Blood ◽  
The Face ◽  
The Central Nervous System ◽  
Obesity Hypertension ◽  
And Function

Adult aging in humans is associated with marked and sustained increases in sympathetic nervous system (SNS) activity to several peripheral tissues, including the heart, the gut-liver circulation, and skeletal muscle. This chronic activation of the peripheral SNS likely is, at least in part, a primary response of the central nervous system to stimulate thermogenesis to prevent further fat storage in the face of increasing adiposity with aging. However, as has been proposed in obesity hypertension, this tonic activation of the peripheral SNS has a number of adverse secondary cardiovascular consequences. These include chronic reductions in leg blood flow and vascular conductance, increased tonic support of arterial blood pressure, reduced limb and systemic α-adrenergic vasoconstrictor responsiveness, impaired baroreflex buffering, large conduit artery hypertrophy, and decreased vascular and cardiac responsiveness to β-adrenergic stimulation. These effects of chronic age-associated SNS activation on the structure and function of the cardiovascular system, in turn, may have important implications for the maintenance of physiological function and homeostasis, as well as the risk of developing clinical cardiovascular and metabolic diseases in middle-aged and older adults.

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 Interactions between the central nervous system and pancreatic islet secretions: a historical perspective

2013 ◽  
Vol 37 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Denovan P. Begg ◽  
Stephen C. Woods
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Food Intake ◽  
Gut Hormones ◽  
The Body ◽  
Endocrine Function ◽  
Reduce Food Intake ◽  
Diverse Range ◽  
The Central Nervous System ◽  
The Brain

The endocrine pancreas is richly innervated with sympathetic and parasympathetic projections from the brain. In the mid-20th century, it was established that α-adrenergic activation inhibits, whereas cholinergic stimulation promotes, insulin secretion; this demonstrated the importance of the sympathetic and parasympathetic systems in pancreatic endocrine function. It was later established that insulin injected peripherally could act within the brain, leading to the discovery of insulin and insulin receptors within the brain and the receptor-mediated transport of insulin into the central nervous system from endothelial cells. The insulin receptor within the central nervous system is widely distributed, reflecting insulin's diverse range of actions, including acting as an adiposity signal to reduce food intake and increase energy expenditure, regulation of systemic glucose responses, altering sympathetic activity, and involvement in cognitive function. As observed with central insulin administration, the pancreatic hormones glucagon, somatostatin, pancreatic polypeptide, and amylin can each also reduce food intake. Pancreatic and also gut hormones are released cephalically, in what is an important mechanism to prepare the body for a meal and prevent excessive postprandial hyperglycemia.

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