Macrophage-derived insulin antagonist ImpL2 induces lipoprotein mobilization upon bacterial infection

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F23%3A00580499" target="_blank" >RIV/60077344:_____/23:00580499 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60076658:12310/23:43907144

Výsledek na webu

<a href="https://www.embopress.org/doi/epdf/10.15252/embj.2023114086" target="_blank" >https://www.embopress.org/doi/epdf/10.15252/embj.2023114086</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.15252/embj.2023114086" target="_blank" >10.15252/embj.2023114086</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Macrophage-derived insulin antagonist ImpL2 induces lipoprotein mobilization upon bacterial infection

Popis výsledku v původním jazyce

The immune response is an energy-demanding process that must be coordinated with systemic metabolic changes redirecting nutrients from stores to the immune system. Although this interplay is fundamental for the function of the immune system, the underlying mechanisms remain elusive. Our data show that the pro-inflammatory polarization of Drosophila macrophages is coupled to the production of the insulin antagonist ImpL2 through the activity of the transcription factor HIF1 alpha. ImpL2 production, reflecting nutritional demands of activated macrophages, subsequently impairs insulin signaling in the fat body, thereby triggering FOXO-driven mobilization of lipoproteins. This metabolic adaptation is fundamental for the function of the immune system and an individual's resistance to infection. We demonstrated that analogically to Drosophila, mammalian immune-activated macrophages produce ImpL2 homolog IGFBP7 in a HIF1 alpha-dependent manner and that enhanced IGFBP7 production by these cells induces mobilization of lipoproteins from hepatocytes. Hence, the production of ImpL2/IGFBP7 by macrophages represents an evolutionarily conserved mechanism by which macrophages alleviate insulin signaling in the central metabolic organ to secure nutrients necessary for their function upon bacterial infection.

Název v anglickém jazyce

Macrophage-derived insulin antagonist ImpL2 induces lipoprotein mobilization upon bacterial infection

Popis výsledku anglicky

The immune response is an energy-demanding process that must be coordinated with systemic metabolic changes redirecting nutrients from stores to the immune system. Although this interplay is fundamental for the function of the immune system, the underlying mechanisms remain elusive. Our data show that the pro-inflammatory polarization of Drosophila macrophages is coupled to the production of the insulin antagonist ImpL2 through the activity of the transcription factor HIF1 alpha. ImpL2 production, reflecting nutritional demands of activated macrophages, subsequently impairs insulin signaling in the fat body, thereby triggering FOXO-driven mobilization of lipoproteins. This metabolic adaptation is fundamental for the function of the immune system and an individual's resistance to infection. We demonstrated that analogically to Drosophila, mammalian immune-activated macrophages produce ImpL2 homolog IGFBP7 in a HIF1 alpha-dependent manner and that enhanced IGFBP7 production by these cells induces mobilization of lipoproteins from hepatocytes. Hence, the production of ImpL2/IGFBP7 by macrophages represents an evolutionarily conserved mechanism by which macrophages alleviate insulin signaling in the central metabolic organ to secure nutrients necessary for their function upon bacterial infection.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

EMBO Journal

ISSN

0261-4189

e-ISSN

1460-2075

Svazek periodika

42

Číslo periodika v rámci svazku

OCT

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

26

Strana od-do

e114086

Kód UT WoS článku

001082872700001

EID výsledku v databázi Scopus

2-s2.0-85173942783