Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction
In: ISSN: 2379-3708 ; JCI Insight ; https://hal.science/hal-04199061 ; JCI Insight, 2023, 2023
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academicJournal
Zugriff:
International audience ; Adipose tissue macrophages (ATMs) play an important role in obesity and inflammation, and they accumulate in adipose tissue (AT) with aging. Furthermore, increased ATM senescence has been shown in obesity-related AT remodeling and dysfunction. However, ATM senescence and its role are unclear in age-related AT dysfunction. Here, we show that ATMs (a) acquire a senescence-like phenotype during chronological aging; (b) display a global decline of basic macrophage functions such as efferocytosis, an essential process to preserve AT homeostasis by clearing dysfunctional or apoptotic cells; and (c) promote AT remodeling and dysfunction. Importantly, we uncover a major role for the age-associated accumulation of osteopontin (OPN) in these processes in visceral AT. Consistently, loss or pharmacologic inhibition of OPN and bone marrow transplantation of OPN-/- mice attenuate the ATM senescence-like phenotype, preserve efferocytosis, and finally restore healthy AT homeostasis in the context of aging. Collectively, our findings implicate pharmacologic OPN inhibition as a viable treatment modality to counter ATM senescence-mediated AT remodeling and dysfunction during aging.
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Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction
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Autor/in / Beteiligte Person: | Sawaki, Daigo ; Zhang, Yanyan ; Mohamadi, Amel ; Pini, Maria ; Mezdari, Zaineb ; Lipskaia, Larissa ; Naushad, Suzain ; Lamendour, Lucille ; Altintas, Dogus Murat ; Breau, Marielle ; Liang, Hao ; Halfaoui, Maissa ; Delmont, Thaïs ; Surenaud, Mathieu ; Rousseau, Déborah ; Yoshimitsu, Takehiko ; Louache, Fawzia ; Adnot, Serge ; Henegar, Corneliu ; Gual, Philippe ; Czibik, Gabor ; Derumeaux, Geneviève ; IMRB - SMCD/"Senescence, Metabolism and Cardiovascular Diseases" Créteil (U955 Inserm - UPEC) ; Institut Mondor de Recherche Biomédicale (IMRB) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) ; IMRB - PGD/"Pathophysiology of Glomerular Diseases" Créteil (U955 Inserm - UPEC) ; IMRB - "From pathophysiology towards immune-basedinterventions in HIV infection" Créteil (U955 Inserm - UPEC) ; IMRB - "Transfusion et Maladies du Globule Rouge" Créteil (U955 Inserm - UPEC) ; Département de physiologie (CHU Henri Mondor) ; Hôpital Henri Mondor ; RHU CARMMA grant and Fondation pour la Recherche Médicale (EQU202003010186) |
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Zeitschrift: | ISSN: 2379-3708 ; JCI Insight ; https://hal.science/hal-04199061 ; JCI Insight, 2023, 2023 |
Veröffentlichung: | HAL CCSD ; American Society for Clinical Investigation, 2023 |
Medientyp: | academicJournal |
DOI: | 10.1172/jci.insight.145811 |
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