Protein-responsive gut hormone tachykinin directs food choice and impacts lifespan

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Animals select food based on hungers that reflect dynamic macronutrient needs, but the hormonal mechanisms underlying nutrient-specific appetite regulation remain poorly defined. Here, we identify tachykinin (Tk) as a protein-responsive gut hormone in Drosophila and female mice, regulated by conserved environmental nutrient-sensing mechanisms. Protein intake activates Tk-expressing enteroendocrine cells (EECs), driving release of Tk through involving target rapamycin (TOR) transient receptor potential A1 (TrpA1). In flies, delineate pathway which controls selective sleep after protein ingestion, mediated glucagon-like adipokinetic (AKH) signalling to neurons adipose tissue. This mechanism suppresses appetite, promotes sugar hunger modulates wakefulness align behaviour with nutritional needs. Inhibiting prolongs lifespan AKH, revealing role for nutrient-dependent longevity. Our results provide framework understanding EEC-derived satiety signals hormones regulating choice, lifespan.

Language: Английский

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Intestinal Enteroendocrine Cells: Present and Future Druggable Targets

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8836 - 8836

Published: May 16, 2023

Enteroendocrine cells are specialized secretory lineage in the small and large intestines that secrete hormones peptides response to luminal contents. The various can act upon neighboring as part of endocrine system, circulate systemically via immune enteric nervous system. Locally, enteroendocrine have a major role gastrointestinal motility, nutrient sensing, glucose metabolism. Targeting intestinal or mimicking hormone secretion has been an important field study obesity other metabolic diseases. Studies on importance these inflammatory auto-immune diseases only recently reported. rapid global increase suggests increased understanding novel therapies needed. This review will focus association between changes disease progression conclude with future potential druggable targets.

Language: Английский

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Enteroendocrine cell regulation of the gut-brain axis

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Nov. 7, 2023

Enteroendocrine cells (EECs) are an essential interface between the gut and brain that communicate signals about nutrients, pain, even information from our microbiome. EECs hormone-producing expressed throughout gastrointestinal epithelium have been leveraged by pharmaceuticals like semaglutide (Ozempic, Wegovy), terzepatide (Mounjaro), retatrutide (Phase 2) for diabetes weight control, linaclotide (Linzess) to treat irritable bowel syndrome (IBS) visceral pain. This review focuses on role of intestinal lumen brain. Canonically, environment through a variety hormones, dividing into separate classes based hormone each cell type secretes. Recent studies revealed more diverse profiles communication modalities including direct synaptic with peripheral neurons. known as neuropod rapidly relay via vagal primary sensory Further, this discusses complex processing machinery within EECs, receptors transduce intraluminal ion channel complement govern initiation propagation these signals. Deeper understanding EEC physiology is necessary safely devastating pervasive conditions obesity.

Language: Английский

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Mechanisms underlying the gut–brain communication: How enterochromaffin (EC) cells activate vagal afferent nerve endings in the small intestine

The Journal of Comparative Neurology, Journal Year: 2024, Volume and Issue: 532(4)

Published: April 1, 2024

Abstract How the gastrointestinal tract communicates with brain, via sensory nerves, is of significant interest for our understanding human health and disease. Enterochromaffin (EC) cells in gut mucosa release a variety neurochemicals, including largest quantity 5‐hydroxytryptamine (5‐HT) body. 5‐HT other substances released from EC activate nerve endings wall remains major unresolved mystery. We used vivo anterograde tracing nodose ganglia to determine spatial relationship between synthesizing peptide‐YY (PYY)‐synthesizing their proximity vagal afferent that project mouse small intestine. The shortest mean distances single 5‐HT‐ PYY‐synthesizing nearest were 33.1 ± 14.4 µm ( n = 56; N 6) 70.3 32.3 16; 6). No morphological evidence was found suggest or PYY‐containing form close associations afferents endings, varicose axons passage. large are many hundreds times greater than those known underlie synaptic transmission nervous system (typically 10–15 nm). Taken together, findings lead inescapable conclusion communication 5‐HT‐containing intestinal occurs paracrine fashion, diffusion. New Noteworthy None here consistent view physical contacts occur Rather, gut–brain passive data presented do not support physically enough communicate fast transmission.

Language: Английский

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Sensory spinal interoceptive pathways and energy balance regulation

Molecular Metabolism, Journal Year: 2023, Volume and Issue: 78, P. 101817 - 101817

Published: Oct. 7, 2023

Interoception plays an important role in homeostatic regulation of energy intake and metabolism. Major interoceptive pathways include gut-to-brain adipose tissue-to brain signaling via vagal sensory nerves hormones, such as leptin. However, spinal neurons is rapidly emerging additional pathway. Here we provide in-depth review the known anatomy functions discuss potential mechanisms relevant for balance homeostasis health disease. Because innervation by dorsal root ganglia (DRG) goes far beyond vagally innervated viscera includes tissue, skeletal muscle, skin, it a position to much more complete metabolic information brain. Molecular anatomical identification function specific DRG will be steps designing pharmacological neuromodulation approaches affect disease states obesity, diabetes, cancer.

Language: Английский

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Neuroendocrine gut–brain signaling in obesity

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

The past decades have witnessed the rise and fall of several, largely unsuccessful, therapeutic attempts to bring escalating obesity pandemic a halt. Looking back look ahead, field has now put its highest hopes in translating insights from how gastrointestinal (GI) tract communicates with brain calibrate behavior, physiology, metabolism. A major focus this review is summarize latest advances comprehending neuroendocrine aspects so-called 'gut-brain axis' explore novel concepts, cutting-edge technologies, recent paradigm-shifting experiments. These exciting continue refine our understanding gut-brain crosstalk are poised promote development additional avenues at dawn new era antiobesity therapeutics.

Language: Английский

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Single-cell transcriptomic atlas of enteroendocrine cells along the murine gastrointestinal tract

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(10), P. e0308942 - e0308942

Published: Oct. 8, 2024

Enteroendocrine cells (EECs) produce over 20 gut hormones which contribute to intestinal physiology, nutrient metabolism and the regulation of food intake. The objective this study was generate a comprehensive transcriptomic map mouse EECs from stomach rectum.

Language: Английский

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Enteroendocrine cells regulate intestinal homeostasis and epithelial function

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 593, P. 112339 - 112339

Published: Aug. 5, 2024

Enteroendocrine cells (EECs) are well-known for their systemic hormonal effects, especially in the regulation of appetite and glycemia. Much less is known about how products made by EECs regulate local environment within intestine. Here, we focus on paracrine interactions between other intestinal as they three essential aspects homeostasis physiology: 1) stem cell function proliferation; 2) nutrient absorption; 3) mucosal barrier function. We also discuss ability to express multiple hormones, describe vitro vivo models study EECs, consider altered GI disease.

Language: Английский

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A neural mechanism for learning from delayed postingestive feedback

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 10, 2023

Animals learn the value of foods based on their postingestive effects and thereby develop aversions to that are toxic

Language: Английский

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The Coding Logic of Interoception

Annual Review of Physiology, Journal Year: 2023, Volume and Issue: 86(1), P. 301 - 327

Published: Dec. 7, 2023

Interoception, the ability to precisely and timely sense internal body signals, is critical for life. The interoceptive system monitors a large variety of mechanical, chemical, hormonal, pathological cues using specialized organ cells, innervating neurons, brain sensory neurons. It important maintaining homeostasis, providing motivational drives, regulating autonomic, cognitive, behavioral functions. However, compared external systems, our knowledge about how diverse signals are coded at level quite limited. In this review, we focus on unique features organization system, with goal better understanding coding logic interoception.

Language: Английский

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