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

Guangming Ding,

Yingge Li, Cheng Chen

et al.

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

Published: Oct. 29, 2024

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, however, 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 identify -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

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

Guangming Ding,

Yingge Li, Cheng Chen

et al.

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
Dietary amino acids promote glucagon-like hormone release to generate global calcium waves in adipose tissues in Drosophila DOI Creative Commons
Muhammad Ahmad,

Shang Wu,

Shengyao Luo

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Propagation of intercellular calcium waves through tissues has been found to coordinate different multicellular responses. Nevertheless, our understanding how operate remains limited. In this study, we explore the real-time dynamics in Drosophila adipose tissues. We identify Adipokinetic Hormone (AKH), fly functional homolog glucagon, as key factor driving Ca2+ activities tissue. find that AKH, which is released into hemolymph from AKH-producing neurosecretory cells, stimulates larval fat by a previously unrecognized gap-junction-independent mechanism promote lipolysis. adult body, however, gap-junction-dependent are triggered presumably uniformly diffused AKH. Additionally, discover amino acids activate leading increased intracellular and AKH secretion. Altogether, show dietary regulate release cells brain, subsequently tissue, enhancing lipid metabolism. Intercellular (ICWs) responses, although precise mechanisms less understood. Here, authors nutrient-triggered hormone brain ICWs

Language: Английский

Citations

0
Knockdown of the adipokinetic hormone receptor inhibits the reproduction of female Culex pipiens pallens (Diptera: Culicidae) by downregulating L‐homoserine and serotonin levels DOI
Xin Wang,

R. D. H. Chu,

Siyao Li

et al.

Insect Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 27, 2025

Abstract The adipokinetic hormone (AKH) receptor, interacting with AKH, regulates the metabolism of amino acids, carbohydrates, and lipids. AKH receptor is abundant in mosquito primary secondary sexual organs; however, exact role reproductive processes specific mechanisms involved are unclear. Among different tissues adult female mosquitoes ( Culex pipiens pallens ), ovaries fat body showed high expression gene. Silencing this gene led to anti‐reproductive effects, including abnormal ovarian morphology, reduced follicle number, a decreased egg‐laying count. Meanwhile, yolk accumulation iron deposition during vitellogenesis phase were observed, accompanied by levels vitellogenin‐A1 precursor transferrin Liquid chromatography‐mass spectrometry analysis revealed decrease L‐homoserine serotonin following knockdown, supplementation above 2 metabolites partly rescued phenotype increased knockdown mosquitoes. Consistent results, Relugolix, an inhibitor likewise affected egg production. Herein, we evidence for function potential mechanism reproduction, possibly offering alternative method control

Language: Английский

Citations

0
Sensing of dietary amino acids and regulation of calcium dynamics in adipose tissues through Adipokinetic hormone inDrosophila DOI Open Access
Muhammad Ahmad,

Shang Wu,

Xuan Guo

et al.

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

Published: March 8, 2024

Abstract Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes various obesity-related diseases. Drosophila melanogaster has emerged an excellent model for investigating metabolism its associated disorders. In this study, we used live-cell imaging demonstrate that fly functional homolog mammalian glucagon, Adipokinetic hormone (AKH), secreted from AKH hormone-producing cells (APCs) in corpora cardiaca, stimulates intracellular Ca 2+ waves larval fat body/adipose tissue promote lipid metabolism. Further, show specific dietary amino acids activate APCs, leading increased secretion. Finally, a comparison dynamics adult bodies revealed different mechanisms regulation, highlighting interplay pulses secretion, extracellular diffusion hormone, intercellular communication through gap junctions. Our study underscores suitability powerful exploring real-time nutrient inter-organ dynamics.

Language: Английский

Citations

1
Dietary Amino Acids Promote Glucagon-like Hormone Release to Generate Novel Calcium Waves in Adipose Tissues DOI Creative Commons
Li He, Muhammad Ahmad,

Shang Wu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 12, 2024

Abstract Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes various obesity-related morbidities. Among different regulatory signals, cytosolic Ca2+ plays pivotal roles in regulation, including glycolysis, gluconeogenesis, lipolysis. Recently, intercellular calcium waves (ICWs), propagation signaling through tissues, have been found systems coordinate multicellular responses. Nevertheless, our understanding how ICWs modulated operate within living organisms remains limited. In this study, we explore real-time dynamics, both organ culture free-behaving Drosophila larval adult adipose tissues. We identified Adipokinetic hormone (AKH), fly functional homolog mammalian glucagon, key factor driving activities adipose tissue. Interestingly, that AKH, which is released a pulsatile manner into circulating hemolymph from AKH-producing neurosecretory cells (APCs) brain, stimulates larval fat by previously unrecognized gap-junction-independent mechanism promote adult body, however, gap-junction-dependent random triggered presumably uniformly diffused AKH. This highlights stage-specific interplay secretion, extracellular diffusion, communication regulation dynamics. Additionally, discovered specific dietary amino acids activate APCs, leading increased intracellular AKH secretion. Altogether, findings identify regulate release peptides subsequently novel thereby enhancing lipid metabolism.

Language: Английский

Citations

0
A tumor-secreted protein utilizes glucagon release to cause host wasting DOI Creative Commons

Guangming Ding,

Yingge Li, Cheng Chen

et al.

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

Published: Oct. 29, 2024

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, however, 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 identify -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

0