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Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity

Recruitment of activated immune cells into white adipose tissue (WAT) is linked to the development of insulin resistance and obesity, but the mechanism behind this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells controls inflammation and insulin resistance in obesity. Sel...

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Autores principales: Macia, Laurence, Yulyaningsih, Ernie, Pangon, Laurent, Nguyen, Amy D., Lin, Shu, Shi, Yan C., Zhang, Lei, Bijker, Martijn, Grey, Shane, Mackay, Fabienne, Herzog, Herbert, Sainsbury, Amanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501846/
https://www.ncbi.nlm.nih.gov/pubmed/23011592
http://dx.doi.org/10.2337/db12-0156
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author Macia, Laurence
Yulyaningsih, Ernie
Pangon, Laurent
Nguyen, Amy D.
Lin, Shu
Shi, Yan C.
Zhang, Lei
Bijker, Martijn
Grey, Shane
Mackay, Fabienne
Herzog, Herbert
Sainsbury, Amanda
author_facet Macia, Laurence
Yulyaningsih, Ernie
Pangon, Laurent
Nguyen, Amy D.
Lin, Shu
Shi, Yan C.
Zhang, Lei
Bijker, Martijn
Grey, Shane
Mackay, Fabienne
Herzog, Herbert
Sainsbury, Amanda
author_sort Macia, Laurence
collection PubMed
description Recruitment of activated immune cells into white adipose tissue (WAT) is linked to the development of insulin resistance and obesity, but the mechanism behind this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells controls inflammation and insulin resistance in obesity. Selective deletion of Y1 receptors in the hematopoietic compartment of mice leads to insulin resistance and inflammation in WAT under high fat–fed conditions. This is accompanied by decreased mRNA expression of the anti-inflammatory marker adiponectin in WAT and an increase of the proinflammatory monocyte chemoattractant protein-1 (MCP-1). In vitro, activated Y1-deficient intraperitoneal macrophages display an increased inflammatory response, with exacerbated secretion of MCP-1 and tumor necrosis factor, whereas addition of neuropeptide Y to wild-type macrophages attenuates the release of these cytokines, this effect being blocked by Y1 but not Y2 receptor antagonism. Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased insulin-induced phosphorylation of the insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1. Thus, Y1 signaling in hematopoietic-derived cells such as macrophages is critical for the control of inflammation and insulin resistance in obesity.
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spelling pubmed-35018462013-12-01 Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity Macia, Laurence Yulyaningsih, Ernie Pangon, Laurent Nguyen, Amy D. Lin, Shu Shi, Yan C. Zhang, Lei Bijker, Martijn Grey, Shane Mackay, Fabienne Herzog, Herbert Sainsbury, Amanda Diabetes Obesity Studies Recruitment of activated immune cells into white adipose tissue (WAT) is linked to the development of insulin resistance and obesity, but the mechanism behind this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells controls inflammation and insulin resistance in obesity. Selective deletion of Y1 receptors in the hematopoietic compartment of mice leads to insulin resistance and inflammation in WAT under high fat–fed conditions. This is accompanied by decreased mRNA expression of the anti-inflammatory marker adiponectin in WAT and an increase of the proinflammatory monocyte chemoattractant protein-1 (MCP-1). In vitro, activated Y1-deficient intraperitoneal macrophages display an increased inflammatory response, with exacerbated secretion of MCP-1 and tumor necrosis factor, whereas addition of neuropeptide Y to wild-type macrophages attenuates the release of these cytokines, this effect being blocked by Y1 but not Y2 receptor antagonism. Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased insulin-induced phosphorylation of the insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1. Thus, Y1 signaling in hematopoietic-derived cells such as macrophages is critical for the control of inflammation and insulin resistance in obesity. American Diabetes Association 2012-12 2012-11-15 /pmc/articles/PMC3501846/ /pubmed/23011592 http://dx.doi.org/10.2337/db12-0156 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by -nc-nd/3.0/ (http://creativecommons.org/licenses/by-nc-nd/3.0/) for details.
spellingShingle Obesity Studies
Macia, Laurence
Yulyaningsih, Ernie
Pangon, Laurent
Nguyen, Amy D.
Lin, Shu
Shi, Yan C.
Zhang, Lei
Bijker, Martijn
Grey, Shane
Mackay, Fabienne
Herzog, Herbert
Sainsbury, Amanda
Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity
title Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity
title_full Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity
title_fullStr Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity
title_full_unstemmed Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity
title_short Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity
title_sort neuropeptide y1 receptor in immune cells regulates inflammation and insulin resistance associated with diet-induced obesity
topic Obesity Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501846/
https://www.ncbi.nlm.nih.gov/pubmed/23011592
http://dx.doi.org/10.2337/db12-0156
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