Transcriptional Regulation of Neuropeptide Receptors Decodes Complexity of Peptidergic Modulation of Behavior and Physiology. DOI Creative Commons

SeungHeui Ryu,

Yanan Wei, Zekun Wu

et al.

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

Published: Nov. 23, 2024

ABSTRACT The modulation of complex behaviors in response to environmental and physiological contexts is a fundamental aspect animal biology, with neuropeptides (NPs) playing crucial role this process. This study investigates the transcriptional regulation neuropeptide receptors (NPRs) as mechanism for context-dependent neuropeptidergic physiology behavior. We hypothesize that control NPR genes, rather than NPs themselves, critical determinant behavior physiology. Using multi-faceted approach, including comparative genomics, transcription factor network analysis, empirical validation model organisms such Drosophila melanogaster , we reveal regulatory landscape where expression tightly controlled. Our findings demonstrate genes exhibit higher number enhancers, CTCF-binding sites, open chromatin regions compared NP suggesting greater susceptibility modulation. architecture allows precise over signaling, enabling dynamic context-specific behavioral responses. results highlight importance NPR-expressing cells by mediating effects on show conserved across species, indicating an evolutionarily significant fine-tuning signaling. Furthermore, our provides insights into distinct mechanisms underlying multifunctionality their receptors, offering novel perspective behaviors. In conclusion, advances understanding signaling focusing NPRs. have broad implications development therapeutic strategies targeting systems various neurological disorders.

Language: Английский

Gut-to-brain regulation of Drosophila aging through neuropeptide F, insulin, and juvenile hormone DOI Creative Commons
Jiangtian Chen, Marcela Nouzová, Fernando G. Noriega

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(43)

Published: Oct. 16, 2024

Dietary restriction (DR) slows aging in many animals, while some cases, the sensory signals from diet alone are sufficient to retard or accelerate lifespan. The digestive tract is a candidate location sense nutrients, where neuropeptides secreted by enteroendocrine cells (EEC) produce systemic response food. Here, we measure how Drosophila neuropeptide F (NPF) into adult circulation EEC and find that specific differentially respond dietary sugar yeast. Female lifespan increased when gut NPF genetically depleted, this manipulation blunt longevity benefit conferred DR. Depletion of receptors at insulin-producing neurons brain also increases female lifespan, consistent with observations loss decreases neuronal insulin secretion. repressing reversed treating adults juvenile hormone (JH) analog. JH produced corpora allata, inhibition receptor tissue titer extends both males females, restored wild type Overall, modulate through interorgan communication mediated gut–brain–corpora allata axis, impacts its control titer. These data suggest consider human incretins their analogs, which used treat obesity diabetes, may impact aging.

Language: Английский

Citations

4
The role of gut–islet axis in pancreatic islet function and glucose homeostasis DOI Creative Commons
Qi Chen,

Yuanyuan Gao,

Fangyu Li

et al.

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Abstract The gastrointestinal tract plays a vital role in the occurrence and treatment of metabolic diseases. Recent studies have convincingly demonstrated bidirectional axis communication between gut islets, enabling to influence glucose metabolism energy homeostasis animals strongly. ‘gut–islet axis’ is an essential endocrine signal that regulates islet function through dialogue intestinal microecology metabolism. discovery glucagon‐like peptide‐1 (GLP‐1), gastric inhibitory peptide (GIP) other hormones has initially set up bridge cells. However, factors remains largely unknown, such as microbiota integrity barrier. Although primarily resides affect function, they also extra‐intestinal organs by absorbing transferring metabolites derived from microorganisms. As result this transfer, islets may be continuously exposed gut‐derived components. Changes composition can damage barrier varying degrees, resulting increased permeability bacteria their derivatives. All these changes contribute severe disturbance critical pathways peripheral tissues organs. In review, we outlined different gut–islet signalling mechanisms associated with summarized latest progress complex molecules microbiota. addition, will discuss impact renin–angiotensin system (RAS) on various components regulate homeostasis. This work indicates therapeutic approaches aiming restore microbial homeostasis, probiotics faecal transplantation (FMT), shown great potential improving outcomes, enhancing patient prognosis slowing down disease progression. Future research should further uncover molecular links explore individualized strategies, which provide innovative perspective approach for diagnosis

Language: Английский

Citations

0
From sensory organs to internal pathways: A comprehensive review of amino acid sensing in Drosophila DOI
Yi Quan, Liangyao Xiong

Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology, Journal Year: 2025, Volume and Issue: unknown, P. 111828 - 111828

Published: Feb. 1, 2025

Language: Английский

Citations

0
A gut hormone governing protein appetite and longevity DOI
Chisako Sakuma, Fumiaki Obata

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

Published: April 14, 2025

Language: Английский

Citations

0
A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster DOI Creative Commons
Yuto Yoshinari, T. Nishimura, Taishi Yoshii

et al.

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

Published: Dec. 30, 2024

Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to deficiency are well-studied, there a significant gap in our understanding of how organisms adaptively suppress intake. In the present study, utilizing fruit fly, Drosophila melanogaster, we discover that peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells response high-protein diet (HPD), vital suppressing overconsumption protein. Gut-derived CCHa1 received small subset enteric neurons produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment CCHa1-mediated gut-enteric neuronal axis results ammonia accumulation and shortened lifespan under HPD conditions. Collectively, findings unravel crosstalk gut pathways orchestrate physiological responses prevent adapt dietary overload.

Language: Английский

Citations

3
Gut-to-brain regulation ofDrosophilaaging through neuropeptide F, insulin and juvenile hormone DOI
Jiangtian Chen, Marcela Nouzová, Fernando G. Noriega

et al.

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

Published: June 30, 2024

Dietary restriction slows aging in many animals, while some cases the sensory signals from diet alone are sufficient to retard or accelerate lifespan. The digestive tract is a candidate location sense nutrients, where neuropeptides secreted by enteroendocrine cells (EEC) produce systemic response food. Here we measure how

Language: Английский

Citations

1
mGluR7: the new player protecting the central nervous system DOI
Li Pan,

Wangrui Lei,

Yushu Dong

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 102, P. 102554 - 102554

Published: Oct. 24, 2024

Language: Английский

Citations

1
The transcription factor Chronophage/BCL11A/B promotes intestinal stem cell proliferation and endocrine differentiation in theDrosophilaintestine DOI Creative Commons

E. KING,

Eleanor Jacobsen,

Nicholas Woolner

et al.

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

Published: Aug. 6, 2024

Abstract Tissue-resident Adult Stem Cells (ASCs) need to continuously adapt their rate of division and differentiation based on tissue environment. However, the gene regulatory networks that govern these decisions in ASCs how they respond challenges such as infection are often not fully understood. We identify a novel role for transcription factor (TF) Chronophage (Cph) ISC proliferation entero-endocrine (EE) cell differentiation. Cph is Z2H2 zinc TF orthologous mammalian BCL11A/B involved regulating adult stem fate various contexts. show here expressed ISCs EEs Drosophila intestine. Increased levels correlates with increased EE cph loss-of-function leads impaired proliferation. elevated during tumourigenesis well ageing conditions. Knockdown Notch-mutant tumour model reduces size incidence extends lifespan. Mechanistically, overexpression an increase enteroendocrine cells DamID DNA-binding qRT-PCR analysis reveals directly regulates key genes Prospero ( pros ) Phyllopod phyl ). In addition, core cycle regulators E2F1 Nerfin-1 controls maintenance. Together, data support finetuning balance between

Language: Английский

Citations

0
Context-dependent impact of the dietary non-essential amino acid tyrosine on Drosophila physiology and longevity DOI Creative Commons
Hina Kosakamoto, Chisako Sakuma,

Rina Okada

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(35)

Published: Aug. 30, 2024

Dietary protein intake modulates growth, reproduction, and longevity by stimulating amino acid (AA)-sensing pathways. Essential AAs are often considered as limiting nutrients during scarcity, the role of dietary non-essential (NEAAs) is less explored. Although tyrosine has been reported to be crucial for sensing restriction in

Language: Английский

Citations

0
Transcriptional Regulation of Neuropeptide Receptors Decodes Complexity of Peptidergic Modulation of Behavior and Physiology. DOI Creative Commons

SeungHeui Ryu,

Yanan Wei, Zekun Wu

et al.

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

Published: Nov. 23, 2024

ABSTRACT The modulation of complex behaviors in response to environmental and physiological contexts is a fundamental aspect animal biology, with neuropeptides (NPs) playing crucial role this process. This study investigates the transcriptional regulation neuropeptide receptors (NPRs) as mechanism for context-dependent neuropeptidergic physiology behavior. We hypothesize that control NPR genes, rather than NPs themselves, critical determinant behavior physiology. Using multi-faceted approach, including comparative genomics, transcription factor network analysis, empirical validation model organisms such Drosophila melanogaster , we reveal regulatory landscape where expression tightly controlled. Our findings demonstrate genes exhibit higher number enhancers, CTCF-binding sites, open chromatin regions compared NP suggesting greater susceptibility modulation. architecture allows precise over signaling, enabling dynamic context-specific behavioral responses. results highlight importance NPR-expressing cells by mediating effects on show conserved across species, indicating an evolutionarily significant fine-tuning signaling. Furthermore, our provides insights into distinct mechanisms underlying multifunctionality their receptors, offering novel perspective behaviors. In conclusion, advances understanding signaling focusing NPRs. have broad implications development therapeutic strategies targeting systems various neurological disorders.

Language: Английский

Citations

0