Spenito-dependent metabolic sexual dimorphism intrinsic to fat storage cells DOI Open Access
Arely V. Diaz, Daniel Stephenson, Travis Nemkov

et al.

Genetics, Journal Year: 2023, Volume and Issue: 225(3)

Published: Sept. 20, 2023

Metabolism in males and females is distinct. Differences are usually linked to sexual reproduction, with circulating signals (e.g. hormones) playing major roles. In contrast, sex differences prior maturity intrinsic individual metabolic tissues less understood. We analyzed Drosophila melanogaster larvae find that store more fat than females, the opposite of dimorphism adults. show storage tissue, including many expression genes. Our previous work identified roles for Spenito (Nito), a conserved RNA-binding protein regulator determination. Nito knockdown specifically tissue abolished between females. further required sex-specific master determination, Sex-lethal (Sxl). "Feminization" cells via tissue-specific overexpression Sxl target gene made lean, reduced induced female-like expression. Altogether, this study supports model which autonomously controls dimorphisms differential genes part through its regulation determination pathway.

Language: Английский

The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster DOI Creative Commons
Yuto Yoshinari, Hina Kosakamoto, Takumi Kamiyama

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Aug. 10, 2021

Abstract The enteroendocrine cell (EEC)-derived incretins play a pivotal role in regulating the secretion of glucagon and insulins mammals. Although glucagon-like insulin-like hormones have been found across animal phyla, incretin-like EEC-derived not yet characterised invertebrates. Here, we show that midgut-derived hormone, neuropeptide F (NPF), acts as sugar-responsive, hormone fruit fly, Drosophila melanogaster . Secreted NPF is received by receptor corpora cardiaca insulin-producing cells. NPF-NPFR signalling resulted suppression production enhancement peptide secretion, eventually promoting lipid anabolism. Similar to loss incretin function mammals, midgut led significant metabolic dysfunction, accompanied lipodystrophy, hyperphagia, hypoglycaemia. These results suggest regulate sugar-dependent metabolism through only mammals but also insects.

Language: Английский

Citations

95
A gut-derived hormone suppresses sugar appetite and regulates food choice in Drosophila DOI Creative Commons
Alina Malita,

Olga I. Kubrak,

Takashi Koyama

et al.

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

Citations

61
Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions DOI Creative Commons
Dick R. Nässel, Meet Zandawala

Open Biology, Journal Year: 2022, Volume and Issue: 12(7)

Published: July 1, 2022

Plasticity in animal behaviour relies on the ability to integrate external and internal cues from changing environment hence modulate activity synaptic circuits of brain. This context-dependent neuromodulation is largely based non-synaptic signalling with neuropeptides. Here, we describe select peptidergic systems Drosophila brain that act at different levels a hierarchy associated physiology. These regions, such as central complex mushroom bodies, which supervise specific behaviours. At top level there are small numbers large neurons arborize widely multiple areas orchestrate or global state manner. bottom local provide executive sensory gain intrinsically restricted parts neuronal circuits. The orchestrating receive interoceptive signals mediate energy sleep homeostasis, metabolic circadian timing, well affect food search, aggression mating. Some these can be triggers conflicting behaviours mating versus aggression, feeding, participate circuits, enabling choices switches.

Language: Английский

Citations

55
Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion DOI Creative Commons
J. Gao, Song Zhang, Pan Deng

et al.

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

Published: April 25, 2024

Abstract Amino acid availability is monitored by animals to adapt their nutritional environment. Beyond gustatory receptors and systemic amino sensors, enteroendocrine cells (EECs) are believed directly percept dietary acids secrete regulatory peptides. However, the cellular machinery underlying acid-sensing EECs how EEC-derived hormones modulate feeding behavior remain elusive. Here, developing tools specifically manipulate EECs, we find that Drosophila neuropeptide F (NPF) from mated female inhibits feeding, similar human PYY. Mechanistically, L-Glutamate acts through metabotropic glutamate receptor mGluR decelerate calcium oscillations in thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive relay an anorexigenic signal brain. Thus, our findings provide mechanistic insights into assess food quality identify a conserved mode of action explains gut NPF/PYY modulates intake.

Language: Английский

Citations

10
Leptin- and cytokine-like unpaired signaling in Drosophila DOI
Meet Zandawala, Jayati Gera

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 584, P. 112165 - 112165

Published: Jan. 23, 2024

Language: Английский

Citations

9
Protein-responsive gut hormone tachykinin directs food choice and impacts lifespan DOI Creative Commons
Nadja Ahrentløv,

Olga I. Kubrak,

Mette Lassen

et al.

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

Citations

1
The insect somatostatin pathway gates vitellogenesis progression during reproductive maturation and the post-mating response DOI Creative Commons
Chen Zhang, Anmo J. Kim,

Crisalesandra Rivera-Perez

et al.

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

Published: Feb. 18, 2022

Abstract Vitellogenesis (yolk accumulation) begins upon eclosion and continues through the process of sexual maturation. Upon reaching maturity, vitellogenesis is placed on hold until it induced again by mating. However, mechanisms that gate in response to developmental reproductive signals remain unclear. Here, we have identified neuropeptide allatostatin-C (AstC)-producing neurons both initiation occurs post-eclosion its re-initiation post-mating. During maturation, AstC receive excitatory inputs from Sex Peptide Abdominal Ganglion (SAG) neurons. In mature virgin females, high sustained activity SAG shuts off via continuous activation mating, however, inhibits neurons, leading deactivation As a result, this permits JH biosynthesis progression mated females. Our work has uncovered central neural circuit gates oogenesis.

Language: Английский

Citations

36
Role of short‐chain fatty acids in host physiology DOI Creative Commons
Mingyue Liu,

Yubo Lu,

Guoyu Xue

et al.

Animal Models and Experimental Medicine, Journal Year: 2024, Volume and Issue: 7(5), P. 641 - 652

Published: June 28, 2024

Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between host, SCFAs serve as energy substrates for intestinal epithelial cells maintain homeostasis in immune metabolism influencing epigenetics, activating G protein-coupled receptors, inhibiting pathogenic microbial infections. This review provides a comprehensive summary synthesis offering an overview latest research progress on roles protecting health, enhancing metabolism, mitigating diseases such cancer, obesity, diabetes, modulating gut-brain axis gut-lung axis, promoting bone

Language: Английский

Citations

7
Sex determination gene transformer regulates the male-female difference in Drosophila fat storage via the adipokinetic hormone pathway DOI Creative Commons
Lianna W. Wat, Zahid Sadek Chowdhury, Jason W. Millington

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Oct. 21, 2021

Sex differences in whole-body fat storage exist many species. For example, Drosophila females store more than males. Yet, the mechanisms underlying this sex difference remain incompletely understood. Here, we identify a key role for determination gene transformer ( tra ) regulating male-female storage. Normally, functional Tra protein is present only females, where it promotes female sexual development. We show that loss of reduced storage, whereas gain males augmented Tra’s promoting was largely due to its function neurons, specifically Adipokinetic hormone (Akh)-producing cells (APCs). Our analysis Akh pathway regulation revealed male bias APC activity and function, sex-biased influenced by limiting triglyceride accumulation Importantly, increased activity, genetically manipulating rescued Tra-dependent effects on This identifies sex-specific as one mechanism levels, provides important insight into conserved dimorphism

Language: Английский

Citations

36
Gut AstA mediates sleep deprivation-induced energy wasting in Drosophila DOI Creative Commons
Yingge Li, Xiaoya Zhou, Cheng Chen

et al.

Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: May 23, 2023

Abstract Severe sleep deprivation (SD) has been highly associated with systemic energy wasting, such as lipid loss and glycogen depletion. Despite immune dysregulation neurotoxicity observed in SD animals, whether how the gut-secreted hormones participate SD-induced disruption of homeostasis remains largely unknown. Using Drosophila a conserved model organism, we characterize that production intestinal Allatostatin A (AstA), major gut-peptide hormone, is robustly increased adult flies bearing severe SD. Interestingly, removal AstA gut using specific drivers significantly improves depletion without affecting homeostasis. We reveal molecular mechanisms whereby promotes release an adipokinetic hormone (Akh), insulin counter-regulatory functionally equivalent to mammalian glucagon, mobilize reserves by remotely targeting its receptor AstA-R2 Akh-producing cells. Similar regulation glucagon secretion wasting AstA/galanin also mice. Further, integrating single-cell RNA sequencing genetic validation, uncover results ROS accumulation augment via TrpA1. Altogether, our demonstrate essential roles mediating SD-associated wasting.

Language: Английский

Citations

15