NADPH oxidase 4 in mouse β cells participates in inflammation on chronic nutrient overload

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F24%3A00582386" target="_blank" >RIV/67985823:_____/24:00582386 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10472638 RIV/00216208:11310/24:10472638 RIV/61989592:15110/24:73622312

Výsledek na webu

<a href="https://doi.org/10.1002/oby.23956" target="_blank" >https://doi.org/10.1002/oby.23956</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/oby.23956" target="_blank" >10.1002/oby.23956</a>

Jazyk výsledku

angličtina

Název v původním jazyce

NADPH oxidase 4 in mouse β cells participates in inflammation on chronic nutrient overload

Popis výsledku v původním jazyce

Objective:By exposing mice carrying a deletion of NADPH oxidase isoform 4, NOX4, specifically in pancreatic β cells (βNOX4−/−) to nutrient excess stimulated by a high-fat diet (HFD), this study aimed to elucidate the role of β-cell redox status in the development of meta-inflammation within the diabetic phenotype.Methods:The authors performed basic phenotyping of βNOX4−/− mice on HFD involving insulin and glycemic analyses, histochemistry of adipocytes, indirect calorimetry, and cytokine analyses. To characterize local inflammation, the study used caspase-1 activity assay, interleukin-1β immunochemistry, and real-time polymerase chain reaction during coculturing of β cells with macrophages.Results:The phenotype of βNOX4−/− mice on HFD was not associated with hyperinsulinemia and hyperglycemia but showed accumulation of excessive lipids in epididymal fat and β cells. Surprisingly, mice showed significantly reduced systemic inflammation. Decreased interleukin-1β protein levels and downregulated NLRP3-inflammasome activity were observed on chronic glucose overload in βNOX4−/− isolated islets and NOX4-silenced INS1-E cells resulting in attenuated proinflammatory polarization of macrophages/monocytes in vitro and in situ and reduced local islet inflammation.Conclusions:Experimental evidence suggests that NOX4 pro-oxidant activity in β cells is involved in NLRP3-inflammasome activation during chronic nutrient overload and participates in local inflammatory signaling and perhaps toward peripheral tissues, contributing to a diabetic inflammatory phenotype.

Název v anglickém jazyce

NADPH oxidase 4 in mouse β cells participates in inflammation on chronic nutrient overload

Popis výsledku anglicky

Objective:By exposing mice carrying a deletion of NADPH oxidase isoform 4, NOX4, specifically in pancreatic β cells (βNOX4−/−) to nutrient excess stimulated by a high-fat diet (HFD), this study aimed to elucidate the role of β-cell redox status in the development of meta-inflammation within the diabetic phenotype.Methods:The authors performed basic phenotyping of βNOX4−/− mice on HFD involving insulin and glycemic analyses, histochemistry of adipocytes, indirect calorimetry, and cytokine analyses. To characterize local inflammation, the study used caspase-1 activity assay, interleukin-1β immunochemistry, and real-time polymerase chain reaction during coculturing of β cells with macrophages.Results:The phenotype of βNOX4−/− mice on HFD was not associated with hyperinsulinemia and hyperglycemia but showed accumulation of excessive lipids in epididymal fat and β cells. Surprisingly, mice showed significantly reduced systemic inflammation. Decreased interleukin-1β protein levels and downregulated NLRP3-inflammasome activity were observed on chronic glucose overload in βNOX4−/− isolated islets and NOX4-silenced INS1-E cells resulting in attenuated proinflammatory polarization of macrophages/monocytes in vitro and in situ and reduced local islet inflammation.Conclusions:Experimental evidence suggests that NOX4 pro-oxidant activity in β cells is involved in NLRP3-inflammasome activation during chronic nutrient overload and participates in local inflammatory signaling and perhaps toward peripheral tissues, contributing to a diabetic inflammatory phenotype.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Obesity

ISSN

1930-7381

e-ISSN

1930-739X

Svazek periodika

32

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

339-351

Kód UT WoS článku

001122685600001

EID výsledku v databázi Scopus

2-s2.0-85179336490