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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
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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. |
format | Online Article Text |
id | pubmed-9936978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
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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