Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown
Published: April 14, 2025
Language: Английский
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
Citations
2
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
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
Citations
60
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
56
Cell Research, Journal Year: 2023, Volume and Issue: 33(6), P. 434 - 447
Published: April 13, 2023
Abstract Obesity imposes a global health threat and calls for safe effective therapeutic options. Here, we found that protein-rich diet significantly reduced body fat storage in fruit flies, which was largely attributed to dietary cysteine intake. Mechanistically, increased the production of neuropeptide FMRFamide (FMRFa). Enhanced FMRFa activity simultaneously promoted energy expenditure suppressed food intake through its cognate receptor (FMRFaR), both contributing loss effect. In body, signaling lipolysis by increasing PKA lipase activity. sweet-sensing gustatory neurons, appetitive perception hence We also demonstrated worked similar way mice via FF (NPFF) signaling, mammalian RFamide peptide. addition, or FMRFa/NPFF administration provided protective effect against metabolic stress flies without behavioral abnormalities. Therefore, our study reveals novel target development therapies obesity related diseases.
Language: Английский
Citations
28
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
eLife, Journal Year: 2025, Volume and Issue: 13
Published: Jan. 29, 2025
Insulin plays a key role in metabolic homeostasis. Drosophila insulin-producing cells (IPCs) are functional analogues of mammalian pancreatic beta and release insulin directly into circulation. To investigate the vivo dynamics IPC activity, we quantified effects nutritional internal state changes on IPCs using electrophysiological recordings. We found that strongly modulates activity. activity decreased with increasing periods starvation. Refeeding flies glucose or fructose, two nutritive sugars, significantly increased whereas non-nutritive sugars had no effect. In contrast to feeding, perfusion did not affect This was reminiscent incretin effect, where ingestion drives higher than intravenous application. Contrary IPCs, Diuretic hormone 44-expressing neurons pars intercerebralis (DH44 PI Ns) responded perfusion. Functional connectivity experiments demonstrated these DH44 Ns do while other DH44Ns inhibit them. Hence, populations autonomously systemically sugar-sensing work parallel maintain Accordingly, activating small, satiety-like effect food-searching behavior reduced starvation-induced hyperactivity, hyperactivity. Taken together, demonstrate an integral part modulatory network orchestrates homeostasis adaptive response shifts state.
Language: Английский
Citations
1
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
Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(3)
Published: March 1, 2022
Neuropeptides are the most diverse messenger molecules in metazoans and involved regulation of daily physiology a wide array behaviors. Some neuropeptides their cognate receptors structurally functionally well conserved over evolution bilaterian animals. Among these peptides related to gastrin cholecystokinin (CCK). In mammals, CCK is produced by intestinal endocrine cells brain neurons, regulates gall bladder contractions, pancreatic enzyme secretion, gut functions, satiety food intake. Additionally, plays important roles neuromodulation several circuits that regulate reward, anxiety, aggression sexual behavior. invertebrates, CCK-type (sulfakinins, SKs) are, with few exceptions, neurons only. Common among invertebrates SKs mediate ingestion variety mechanisms. Also secretion digestive enzymes has been reported. Studies genetically tractable fly Drosophila have advanced our understanding SK signaling mechanisms feeding, but also gustatory sensitivity, locomotor activity, reproductive A set eight SK-expressing competing males, they integrate internal state external stimuli diminish sex drive increase aggression. The same sugar gustation, induce reduce feeding. Although functional CCK/SK appear between available data suggest underlying differ.
Language: Английский
Citations
36
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