Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.

Adipose tissue inflammation is a major cause of the pathogenesis of obesity and comorbidities. To study the involvement of M1/M2 cytokine expression of adipose tissue in the regulatory mechanisms of dipeptidyl peptidase 4 (DPP4) and insulin resistance in diabetes, stromal vascular fractions (SVFs) w...

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Autores principales:	Lee-Wei Chen, Pei-Hsuan Chen, Jui-Hung Yen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/25bf716a7a434aab8d7f0410e617444e
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spelling	oai:doaj.org-article:25bf716a7a434aab8d7f0410e617444e2021-11-25T06:23:43ZInhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.1932-620310.1371/journal.pone.0252153https://doaj.org/article/25bf716a7a434aab8d7f0410e617444e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252153https://doaj.org/toc/1932-6203Adipose tissue inflammation is a major cause of the pathogenesis of obesity and comorbidities. To study the involvement of M1/M2 cytokine expression of adipose tissue in the regulatory mechanisms of dipeptidyl peptidase 4 (DPP4) and insulin resistance in diabetes, stromal vascular fractions (SVFs) were purified from inguinal adipose tissue of diabetic (Leprdb/db) and non-diabetic (Lepr+/+) mice followed by analysis of M1/M2 cytokine expression. SVFs of Leprdb/db mice exhibited increased TNF-α, IL-6, IL-1β, CCL2, and DPP4 mRNA expression but decreased IL-10 mRNA expression. Plasma from Leprdb/db mice induced TNF-α, IL-6, IL-1β, CCL2, and DPP4 mRNA expression and plasma from Lepr+/+ mice induced IL-10 mRNA expression in SVFs from Leprdb/db mice. Injection of Lepr+/+ plasma into the adipose tissue of Leprdb/db mice decreased mRNA expression of TNF-α, IL-6, IL-1β, CCL2, and DPP4 and protein expression of pJNK and DPP4 in SVFs, reduced mRNA expression of ICAM, FMO3, IL-1β, iNOS, TNF-α, IL-6, and DPP4 and protein expression of ICAM, FMO3, and DPP4 in liver, and suppressed mRNA expression of TNF-α, IL-6, IL-1β, and DPP4 in Kupffer cells. Plasma from Leprdb/db mice did not induce M1 cytokine expression in SVFs from Leprdb/db-Jnk1-/- mice. Altogether, we demonstrate that diabetes induces M1 but decreases M2 cytokine expression in adipose tissue. Diabetic plasma-induced M1 expression is potentially through pJNK signaling pathways. Non-diabetic plasma reverses M1/M2 cytokine expression, plasma CCL2 levels, DPP4 activity, and Kupffer cell activation in diabetes. Our results suggest M1/M2 cytokine expression in adipose tissue is critical in diabetes-induced DPP4 activity, liver inflammation, and insulin resistance.Lee-Wei ChenPei-Hsuan ChenJui-Hung YenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0252153 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lee-Wei Chen Pei-Hsuan Chen Jui-Hung Yen Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.
description	Adipose tissue inflammation is a major cause of the pathogenesis of obesity and comorbidities. To study the involvement of M1/M2 cytokine expression of adipose tissue in the regulatory mechanisms of dipeptidyl peptidase 4 (DPP4) and insulin resistance in diabetes, stromal vascular fractions (SVFs) were purified from inguinal adipose tissue of diabetic (Leprdb/db) and non-diabetic (Lepr+/+) mice followed by analysis of M1/M2 cytokine expression. SVFs of Leprdb/db mice exhibited increased TNF-α, IL-6, IL-1β, CCL2, and DPP4 mRNA expression but decreased IL-10 mRNA expression. Plasma from Leprdb/db mice induced TNF-α, IL-6, IL-1β, CCL2, and DPP4 mRNA expression and plasma from Lepr+/+ mice induced IL-10 mRNA expression in SVFs from Leprdb/db mice. Injection of Lepr+/+ plasma into the adipose tissue of Leprdb/db mice decreased mRNA expression of TNF-α, IL-6, IL-1β, CCL2, and DPP4 and protein expression of pJNK and DPP4 in SVFs, reduced mRNA expression of ICAM, FMO3, IL-1β, iNOS, TNF-α, IL-6, and DPP4 and protein expression of ICAM, FMO3, and DPP4 in liver, and suppressed mRNA expression of TNF-α, IL-6, IL-1β, and DPP4 in Kupffer cells. Plasma from Leprdb/db mice did not induce M1 cytokine expression in SVFs from Leprdb/db-Jnk1-/- mice. Altogether, we demonstrate that diabetes induces M1 but decreases M2 cytokine expression in adipose tissue. Diabetic plasma-induced M1 expression is potentially through pJNK signaling pathways. Non-diabetic plasma reverses M1/M2 cytokine expression, plasma CCL2 levels, DPP4 activity, and Kupffer cell activation in diabetes. Our results suggest M1/M2 cytokine expression in adipose tissue is critical in diabetes-induced DPP4 activity, liver inflammation, and insulin resistance.
format	article
author	Lee-Wei Chen Pei-Hsuan Chen Jui-Hung Yen
author_facet	Lee-Wei Chen Pei-Hsuan Chen Jui-Hung Yen
author_sort	Lee-Wei Chen
title	Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.
title_short	Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.
title_full	Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.
title_fullStr	Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.
title_full_unstemmed	Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.
title_sort	inhibiting adipose tissue m1 cytokine expression decreases dpp4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/25bf716a7a434aab8d7f0410e617444e
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_version_	1718413729721221120

Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model.

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