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Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis

Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low‐grade inflammation that contributes to the development of diabetes, steatosis, and insulin resistance. Recent research has shown that this chronic inflammation is crucially dependent on p38 pathway...

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Autores principales: Crespo, María, Nikolic, Ivana, Mora, Alfonso, Rodríguez, Elena, Leiva‐Vega, Luis, Pintor‐Chocano, Aránzazu, Horrillo, Daniel, Hernández‐Cosido, Lourdes, Torres, Jorge L., Novoa, Eva, Nogueiras, Rubén, Medina‐Gómez, Gema, Marcos, Miguel, Leiva, Magdalena, Sabio, Guadalupe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936978/
https://www.ncbi.nlm.nih.gov/pubmed/35592906
http://dx.doi.org/10.1002/hep.32581
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author Crespo, María
Nikolic, Ivana
Mora, Alfonso
Rodríguez, Elena
Leiva‐Vega, Luis
Pintor‐Chocano, Aránzazu
Horrillo, Daniel
Hernández‐Cosido, Lourdes
Torres, Jorge L.
Novoa, Eva
Nogueiras, Rubén
Medina‐Gómez, Gema
Marcos, Miguel
Leiva, Magdalena
Sabio, Guadalupe
author_facet Crespo, María
Nikolic, Ivana
Mora, Alfonso
Rodríguez, Elena
Leiva‐Vega, Luis
Pintor‐Chocano, Aránzazu
Horrillo, Daniel
Hernández‐Cosido, Lourdes
Torres, Jorge L.
Novoa, Eva
Nogueiras, Rubén
Medina‐Gómez, Gema
Marcos, Miguel
Leiva, Magdalena
Sabio, Guadalupe
author_sort Crespo, María
collection PubMed
description Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low‐grade inflammation that contributes to the development of diabetes, steatosis, and insulin resistance. Recent research has shown that this chronic inflammation is crucially dependent on p38 pathway activity in macrophages, suggesting p38 inhibition as a possible treatment for obesity comorbidities. Nevertheless, we report here that lack of p38 activation in myeloid cells worsens high‐fat diet–induced obesity, diabetes, and steatosis. Deficient p38 activation increases macrophage IL‐12 production, leading to inhibition of hepatic FGF21 and reduction of thermogenesis in the brown fat. The implication of FGF21 in the phenotype was confirmed by its specific deletion in hepatocytes. We also found that IL‐12 correlates with liver damage in human biopsies, indicating the translational potential of our results. Our findings suggest that myeloid p38 has a dual role in inflammation and that drugs targeting IL‐12 might improve the homeostatic regulation of energy balance in response to metabolic stress.
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spelling pubmed-99369782023-02-18 Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis Crespo, María Nikolic, Ivana Mora, Alfonso Rodríguez, Elena Leiva‐Vega, Luis Pintor‐Chocano, Aránzazu Horrillo, Daniel Hernández‐Cosido, Lourdes Torres, Jorge L. Novoa, Eva Nogueiras, Rubén Medina‐Gómez, Gema Marcos, Miguel Leiva, Magdalena Sabio, Guadalupe Hepatology Original Articles: Steatohepatitis Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low‐grade inflammation that contributes to the development of diabetes, steatosis, and insulin resistance. Recent research has shown that this chronic inflammation is crucially dependent on p38 pathway activity in macrophages, suggesting p38 inhibition as a possible treatment for obesity comorbidities. Nevertheless, we report here that lack of p38 activation in myeloid cells worsens high‐fat diet–induced obesity, diabetes, and steatosis. Deficient p38 activation increases macrophage IL‐12 production, leading to inhibition of hepatic FGF21 and reduction of thermogenesis in the brown fat. The implication of FGF21 in the phenotype was confirmed by its specific deletion in hepatocytes. We also found that IL‐12 correlates with liver damage in human biopsies, indicating the translational potential of our results. Our findings suggest that myeloid p38 has a dual role in inflammation and that drugs targeting IL‐12 might improve the homeostatic regulation of energy balance in response to metabolic stress. Lippincott Williams & Wilkins 2023-03 2023-02-17 /pmc/articles/PMC9936978/ /pubmed/35592906 http://dx.doi.org/10.1002/hep.32581 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (https://creativecommons.org/licenses/by-nc/4.0/) (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/)
spellingShingle Original Articles: Steatohepatitis
Crespo, María
Nikolic, Ivana
Mora, Alfonso
Rodríguez, Elena
Leiva‐Vega, Luis
Pintor‐Chocano, Aránzazu
Horrillo, Daniel
Hernández‐Cosido, Lourdes
Torres, Jorge L.
Novoa, Eva
Nogueiras, Rubén
Medina‐Gómez, Gema
Marcos, Miguel
Leiva, Magdalena
Sabio, Guadalupe
Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis
title Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis
title_full Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis
title_fullStr Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis
title_full_unstemmed Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis
title_short Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis
title_sort myeloid p38 activation maintains macrophage–liver crosstalk and bat thermogenesis through il‐12–fgf21 axis
topic Original Articles: Steatohepatitis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936978/
https://www.ncbi.nlm.nih.gov/pubmed/35592906
http://dx.doi.org/10.1002/hep.32581
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