Cargando…
Modulation of adipose inflammation by cellular retinoic acid-binding protein 1
OBJECTIVES: Obesity, a metabolic syndrome, is known to be related to inflammation, especially adipose tissue inflammation. Cellular interactions within the expanded white adipose tissue (WAT) in obesity contribute to inflammation and studies have suggested that inflammation is triggered by inflamed...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9492549/ https://www.ncbi.nlm.nih.gov/pubmed/35794192 http://dx.doi.org/10.1038/s41366-022-01175-3 |
_version_ | 1784793508253532160 |
---|---|
author | Wei, Chin-Wen Nhieu, Jennifer Lin, Yu-Lung Wei, Li-Na |
author_facet | Wei, Chin-Wen Nhieu, Jennifer Lin, Yu-Lung Wei, Li-Na |
author_sort | Wei, Chin-Wen |
collection | PubMed |
description | OBJECTIVES: Obesity, a metabolic syndrome, is known to be related to inflammation, especially adipose tissue inflammation. Cellular interactions within the expanded white adipose tissue (WAT) in obesity contribute to inflammation and studies have suggested that inflammation is triggered by inflamed adipocytes that recruit M1 macrophages into WAT. What causes accumulation of unhealthy adipocytes is an important topic of investigation. This study aims to understand the action of Cellular Retinoic Acid Binding Protein 1 (CRABP1) in WAT inflammation. METHODS: Eight weeks-old wild type (WT) and Crabp1 knockout (CKO) mice were fed with a normal diet (ND) or high-fat diet (HFD) for 8 weeks. Body weight and food intake were monitored. WATs and serum were collected for cellular and molecular analyses to determine affected signaling pathways. In cell culture studies, primary adipocyte differentiation and bone marrow-derived macrophages (BMDM) were used to examine adipocytes’ effects, mediated by CRABP1, in macrophage polarization. The 3T3L1-adipocyte was used to validate relevant signaling pathways. RESULTS: CKO mice developed an obese phenotype, more severely under high-fat diet (HFD) feeding. Further, CKO’s WAT exhibited a more severe inflammatory state as compared to wild type (WT) WAT, with a significantly expanded M1-like macrophage population. However, this was not caused by intrinsic defects of CKO macrophages. Rather, CKO adipocytes produced a significantly reduced level of adiponectin and had significantly lowered mitochondrial DNA content. CKO adipocyte-conditioned medium, compared to WT control, inhibited M2-like (CD206(+)) macrophage polarization. Mechanistically, defects in CKO adipocytes involved the ERK1/2 signaling pathway that could be modulated by CRABP1. CONCLUSIONS: This study shows that CRABP1 plays a protective role against HFD-induced WAT inflammation through, in part, its regulation of adiponectin production and mitochondrial homeostasis in adipocytes, thereby modulating macrophage polarization in WAT to control its inflammatory potential. |
format | Online Article Text |
id | pubmed-9492549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94925492022-09-23 Modulation of adipose inflammation by cellular retinoic acid-binding protein 1 Wei, Chin-Wen Nhieu, Jennifer Lin, Yu-Lung Wei, Li-Na Int J Obes (Lond) Article OBJECTIVES: Obesity, a metabolic syndrome, is known to be related to inflammation, especially adipose tissue inflammation. Cellular interactions within the expanded white adipose tissue (WAT) in obesity contribute to inflammation and studies have suggested that inflammation is triggered by inflamed adipocytes that recruit M1 macrophages into WAT. What causes accumulation of unhealthy adipocytes is an important topic of investigation. This study aims to understand the action of Cellular Retinoic Acid Binding Protein 1 (CRABP1) in WAT inflammation. METHODS: Eight weeks-old wild type (WT) and Crabp1 knockout (CKO) mice were fed with a normal diet (ND) or high-fat diet (HFD) for 8 weeks. Body weight and food intake were monitored. WATs and serum were collected for cellular and molecular analyses to determine affected signaling pathways. In cell culture studies, primary adipocyte differentiation and bone marrow-derived macrophages (BMDM) were used to examine adipocytes’ effects, mediated by CRABP1, in macrophage polarization. The 3T3L1-adipocyte was used to validate relevant signaling pathways. RESULTS: CKO mice developed an obese phenotype, more severely under high-fat diet (HFD) feeding. Further, CKO’s WAT exhibited a more severe inflammatory state as compared to wild type (WT) WAT, with a significantly expanded M1-like macrophage population. However, this was not caused by intrinsic defects of CKO macrophages. Rather, CKO adipocytes produced a significantly reduced level of adiponectin and had significantly lowered mitochondrial DNA content. CKO adipocyte-conditioned medium, compared to WT control, inhibited M2-like (CD206(+)) macrophage polarization. Mechanistically, defects in CKO adipocytes involved the ERK1/2 signaling pathway that could be modulated by CRABP1. CONCLUSIONS: This study shows that CRABP1 plays a protective role against HFD-induced WAT inflammation through, in part, its regulation of adiponectin production and mitochondrial homeostasis in adipocytes, thereby modulating macrophage polarization in WAT to control its inflammatory potential. Nature Publishing Group UK 2022-07-06 2022 /pmc/articles/PMC9492549/ /pubmed/35794192 http://dx.doi.org/10.1038/s41366-022-01175-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wei, Chin-Wen Nhieu, Jennifer Lin, Yu-Lung Wei, Li-Na Modulation of adipose inflammation by cellular retinoic acid-binding protein 1 |
title | Modulation of adipose inflammation by cellular retinoic acid-binding protein 1 |
title_full | Modulation of adipose inflammation by cellular retinoic acid-binding protein 1 |
title_fullStr | Modulation of adipose inflammation by cellular retinoic acid-binding protein 1 |
title_full_unstemmed | Modulation of adipose inflammation by cellular retinoic acid-binding protein 1 |
title_short | Modulation of adipose inflammation by cellular retinoic acid-binding protein 1 |
title_sort | modulation of adipose inflammation by cellular retinoic acid-binding protein 1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9492549/ https://www.ncbi.nlm.nih.gov/pubmed/35794192 http://dx.doi.org/10.1038/s41366-022-01175-3 |
work_keys_str_mv | AT weichinwen modulationofadiposeinflammationbycellularretinoicacidbindingprotein1 AT nhieujennifer modulationofadiposeinflammationbycellularretinoicacidbindingprotein1 AT linyulung modulationofadiposeinflammationbycellularretinoicacidbindingprotein1 AT weilina modulationofadiposeinflammationbycellularretinoicacidbindingprotein1 |