Dietary regulation in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 23, 2022

Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan delaying ageing various species such as yeast, drosophila, rodent, primate human. It emerges develop precision-nutrition therapeutics slow age-related biological processes treat diverse diseases. However, nutritive advantages frequently diversify among individuals well organs tissues, which brings challenges this field. In review, we summarize different forms of dietary interventions extensively prescribed improvement disease treatment pre-clinical or clinical. We discuss nutrient-mediated mechanisms including metabolic regulators, metabolism pathways, epigenetic circadian clocks. Comparably, describe diet-responsive effectors by influence endocrinic, immunological, microbial neural states responsible improving health preventing multiple diseases humans. Furthermore, expatiate patterns dietotheroapies, fasting, calorie-restricted diet, ketogenic high-fibre plants-based protein restriction diet with specific reduction amino acids microelements, potentially affecting morbid states. Altogether, emphasize profound nutritional therapy, highlight crosstalk explored critical factors individualized therapeutic approaches predictors.

Language: Английский

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A tumor-secreted protein utilizes glucagon release to cause host wasting

Cell Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 10, 2025

Abstract Tumor‒host interaction plays a critical role in malignant tumor-induced organ wasting across multiple species. Despite known regulation of regional individual peripheral organs by tumors, whether and how tumors utilize host catabolic hormone(s) to simultaneously induce systemic wasting, is largely unknown. Using the conserved yki 3SA -tumor model Drosophila , we discovered that increase production adipokinetic hormone (Akh), glucagon-like hormone, cause including muscle dysfunction, lipid loss, hyperglycemia, ovary atrophy. We next integrated RNAi screening Gal4-LexA dual expression system show -gut secrete Pvf1 remotely activate its receptor Pvr Akh-producing cells (APCs), ultimately promoting Akh production. The underlying molecular mechanisms involved Pvf1-Pvr axis triggers Mmp2-dependent ECM remodeling APCs enhances innervation from excitatory cholinergic neurons. Interestingly, also confirmed similar governing glucagon release mammals. Blockade either or PDGFR (homolog Pvr) action efficiently ameliorated presence tumors. Therefore, our results demonstrate promote neural-associated Akh/glucagon via wasting.

Language: Английский

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A gut-derived hormone suppresses sugar appetite and regulates food choice in Drosophila

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(11), P. 1532 - 1550

Published: Nov. 7, 2022

Abstract Animals must adapt their dietary choices to meet nutritional needs. How these needs are detected and translated into nutrient-specific appetites that drive food-choice behaviours is poorly understood. Here we show enteroendocrine cells of the adult female Drosophila midgut sense nutrients in response release neuropeptide F (NPF), which an ortholog mammalian Y-family gut-brain hormones. Gut-derived NPF acts on glucagon-like adipokinetic hormone (AKH) signalling induce sugar satiety increase consumption protein-rich food, adipose tissue promote storage ingested nutrients. Suppression NPF-mediated gut leads overconsumption while simultaneously decreasing intake yeast. Furthermore, gut-derived has a female-specific function promoting protein-containing food mated females. Together, our findings suggest NPF-to-AKH modulates specific regulates choice ensure homeostatic nutrients, providing insight hormonal mechanisms underlie hungers.

Language: Английский

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

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 4, 2022

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 coordinate systemic energy balance. However, gut-derived hormones affecting behavioral responses poorly defined. Here we show that endocrine cells Drosophila gut sense nutrient stress mechanism involves TOR pathway in response secrete peptide hormone allatostatin C, somatostatin homolog. Gut-derived C induces secretion glucagon-like adipokinetic food intake mobilization. Loss Allatostatin or its receptor adipokinetic-hormone-producing impairs lipid sugar mobilization during fasting, leading hypoglycemia. Our findings illustrate nutrient-responsive maintains homeostasis under nutrient-stress conditions, function essential health whose failure can lead disorders.

Language: Английский

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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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NHA1 is a cation/proton antiporter essential for the water-conserving functions of the rectal complex in Tribolium castaneum

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(13)

Published: March 21, 2023

More than half of all extant metazoan species on earth are insects. The evolutionary success insects is linked with their ability to osmoregulate, suggesting that they have evolved unique physiological mechanisms maintain water balance. In beetles (Coleoptera)—the largest group insects—a specialized rectal (“cryptonephridial”) complex has recovers from the rectum destined for excretion and recycles it back body. However, molecular underpinning remarkable water-conserving functions this system unknown. Here, we introduce a transcriptomic resource, BeetleAtlas.org, exceptionally desiccation-tolerant red flour beetle Tribolium castaneum, demonstrate its utility by identifying cation/H + antiporter (NHA1) enriched functionally significant in complex. NHA1 localizes exclusively cell type, leptophragmata, distal region Malpighian tubules associated Computational modeling electrophysiological characterization Xenopus oocytes show acts as an electroneutral K /H antiporter. Furthermore, genetic silencing Nha1 dramatically increases excretory loss reduces organismal survival during desiccation stress, implying activity essential maintaining systemic Finally, Tiptop, conserved transcription factor, regulates expression leptophragmata controls maturation, illuminating developmental mechanism establishes cell. Together, our work provides insights into architecture function one most powerful nature,

Language: Английский

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Mechanisms of Systemic Osmoregulation in Insects

Annual Review of Entomology, Journal Year: 2023, Volume and Issue: 69(1), P. 415 - 438

Published: Sept. 27, 2023

Water is essential to life. Terrestrial insects lose water by evaporation from the body surface and respiratory surfaces, as well in excretory products, posing a challenge made more acute their high surface-to-volume ratio. These losses must be kept minimum offset gained other sources. By contrast, such blood-sucking bug Rhodnius prolixus consume up 10 times weight single blood meal, necessitating rapid expulsion of excess ions. How do manage ion budgets? A century study has revealed great deal about organ systems that use maintain balance regulation. Traditionally, taxonomically wide range species were studied, whereas recent research focused on model organisms leverage power molecular genetic approach. Key advances new technologies have become available for wider past decade. We document how these approaches already begun inform our understanding diversity conservation insect systemic osmoregulation. advocate combined with traditional broader nonmodel gain comprehensive overview mechanism underpinning osmoregulation most species-rich group animals earth, insects.

Language: Английский

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Synaptic connectome of a neurosecretory network in the Drosophila brain

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

Abstract Hormones mediate inter-organ signaling which is crucial in orchestrating diverse behaviors and physiological processes including sleep activity, feeding, growth, metabolism reproduction. The pars intercerebralis lateralis insects represent major hubs contain neurosecretory cells (NSC) that produce various hormones. To obtain insight into how hormonal regulated, we have characterized the synaptic connectome of NSC adult Drosophila brain. Identification neurons providing inputs to multiple subtypes implicates diuretic hormone 44-expressing as a coordinator physiology behavior. Surprisingly, despite most having dendrites subesophageal zone (primary taste processing center), gustatory are largely indirect. We also deciphered pathways via olfactory relayed NSC. Further, our analyses revealed substantial from descending NSC, suggesting regulate both endocrine motor output synchronize changes with appropriate behaviors. In contrast inputs, sparse mostly mediated by corazonin Therefore, additionally determine putative paracrine interconnectivity between peripheral tissues analyzing single-cell transcriptomic datasets. Our comprehensive characterization network provides platform understand complex networks they orchestrate animal physiology.

Language: Английский

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The gonadotropin-releasing hormone (GnRH) superfamily across Pancrustacea/Tetraconata: A role in metabolism?

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 590, P. 112238 - 112238

Published: April 13, 2024

Language: Английский

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A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 23, 2024

Abstract Pancreatic β cells secrete insulin in response to glucose elevation maintain homeostasis. A complex network of inter-organ communication operates modulate secretion and regulate levels after a meal. Lipids obtained from diet or generated intracellularly are known amplify glucose-stimulated secretion, however, the underlying mechanisms not completely understood. Here, we show that Drosophila secretory lipase, Vaha (CG8093), is synthesized midgut moves brain where it concentrates insulin-producing process requiring Lipid Transfer Particle, lipoprotein originating fat body. In dietary fat, stimulates insulin-like peptide release (ILP), deficiency results reduced circulatory ILP diabetic features including hyperglycemia hyperlipidemia. Our findings suggest functions as diacylglycerol lipase physiologically, by being molecular link between lipid amplified gut-brain axis.

Language: Английский

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