Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largel...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ori Nov, Hagit Shapiro, Hilla Ovadia, Tanya Tarnovscki, Irit Dvir, Elad Shemesh, Julia Kovsan, Ilan Shelef, Yaron Carmi, Elena Voronov, Ron N Apte, Eli Lewis, Yulia Haim, Daniel Konrad, Nava Bashan, Assaf Rudich
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/09511dcc0e7c4946be115d467ef91db4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:09511dcc0e7c4946be115d467ef91db4
record_format	dspace
spelling	oai:doaj.org-article:09511dcc0e7c4946be115d467ef91db42021-11-18T08:01:17ZInterleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.1932-620310.1371/journal.pone.0053626https://doaj.org/article/09511dcc0e7c4946be115d467ef91db42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23341960/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF) mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT) transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers), Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI)-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4) that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin sensitivity. Collectively, we demonstrate that by promoting adipose inflammation and limiting fat tissue expandability, IL-1β supports ectopic fat accumulation in hepatocytes and adipose-tissue macrophages, contributing to impaired fat-liver crosstalk in nutritional obesity.Ori NovHagit ShapiroHilla OvadiaTanya TarnovsckiIrit DvirElad ShemeshJulia KovsanIlan ShelefYaron CarmiElena VoronovRon N ApteEli LewisYulia HaimDaniel KonradNava BashanAssaf RudichPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53626 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ori Nov Hagit Shapiro Hilla Ovadia Tanya Tarnovscki Irit Dvir Elad Shemesh Julia Kovsan Ilan Shelef Yaron Carmi Elena Voronov Ron N Apte Eli Lewis Yulia Haim Daniel Konrad Nava Bashan Assaf Rudich Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.
description	The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF) mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT) transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers), Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI)-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4) that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin sensitivity. Collectively, we demonstrate that by promoting adipose inflammation and limiting fat tissue expandability, IL-1β supports ectopic fat accumulation in hepatocytes and adipose-tissue macrophages, contributing to impaired fat-liver crosstalk in nutritional obesity.
format	article
author	Ori Nov Hagit Shapiro Hilla Ovadia Tanya Tarnovscki Irit Dvir Elad Shemesh Julia Kovsan Ilan Shelef Yaron Carmi Elena Voronov Ron N Apte Eli Lewis Yulia Haim Daniel Konrad Nava Bashan Assaf Rudich
author_facet	Ori Nov Hagit Shapiro Hilla Ovadia Tanya Tarnovscki Irit Dvir Elad Shemesh Julia Kovsan Ilan Shelef Yaron Carmi Elena Voronov Ron N Apte Eli Lewis Yulia Haim Daniel Konrad Nava Bashan Assaf Rudich
author_sort	Ori Nov
title	Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.
title_short	Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.
title_full	Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.
title_fullStr	Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.
title_full_unstemmed	Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.
title_sort	interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/09511dcc0e7c4946be115d467ef91db4
work_keys_str_mv	AT orinov interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT hagitshapiro interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT hillaovadia interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT tanyatarnovscki interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT iritdvir interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT eladshemesh interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT juliakovsan interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT ilanshelef interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT yaroncarmi interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT elenavoronov interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT ronnapte interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT elilewis interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT yuliahaim interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT danielkonrad interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT navabashan interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability AT assafrudich interleukin1bregulatesfatlivercrosstalkinobesitybyautoparacrinemodulationofadiposetissueinflammationandexpandability
_version_	1718422586097926144

Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

Ejemplares similares