Lipid-associated macrophages reshape BAT cell identity in obesity.

Autor:	Sciarretta F; IRCCS Santa Lucia Foundation, Rome, Italy., Ninni A; Department of Biology, University of Rome Tor Vergata, Rome, Italy; PhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Rome, Italy., Zaccaria F; Department of Biology, University of Rome Tor Vergata, Rome, Italy; PhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Rome, Italy., Chiurchiù V; Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, Rome, Italy; Institute of Translational Pharmacology, National Research Council, Rome, Italy., Bertola A; Université Côte d'Azur, CNRS, LP2M, Nice, France., Karlinsey K; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT, USA., Jia W; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA., Ceci V; Department of Biology, University of Rome Tor Vergata, Rome, Italy; PhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Rome, Italy., Di Biagio C; Department of Biology, University of Rome Tor Vergata, Rome, Italy., Xu Z; NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA., Gaudioso F; IRCCS Santa Lucia Foundation, Rome, Italy; Department of Biology, University of Rome Tor Vergata, Rome, Italy; PhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Rome, Italy., Tortolici F; Department of Biology, University of Rome Tor Vergata, Rome, Italy., Tiberi M; Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, Rome, Italy., Zhang J; Department of Nutrition & Integrative Physiology, University of Utah, Salt Lake City, UT, USA., Carotti S; Integrated Research Center (PRAAB), Campus Biomedico University of Rome, Rome, Italy., Boudina S; Department of Nutrition & Integrative Physiology, University of Utah, Salt Lake City, UT, USA; Molecular Medicine Program (U2M2), University of Utah, Salt Lake City, UT, USA., Grumati P; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy; Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy., Zhou B; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT, USA., Brestoff JR; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA., Ivanov S; Université Côte d'Azur, CNRS, LP2M, Nice, France., Aquilano K; Department of Biology, University of Rome Tor Vergata, Rome, Italy., Lettieri-Barbato D; Department of Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS Fondazione Bietti, Rome, Italy. Electronic address: daniele.lettieri.barbato@uniroma2.it.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Jul 23; Vol. 43 (7), pp. 114447. Date of Electronic Publication: 2024 Jul 03.
DOI:	10.1016/j.celrep.2024.114447
Abstrakt:	Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity, but the molecular mechanisms that drive BAT cell remodeling remain largely unexplored. Using a multilayered approach, we comprehensively mapped a reorganization in BAT cells. We uncovered a subset of macrophages as lipid-associated macrophages (LAMs), which were massively increased in genetic and dietary model of BAT expansion. LAMs participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically stressed brown adipocytes. CD36 scavenger receptor drove LAM phenotype, and CD36-deficient LAMs were able to increase brown fat genes in adipocytes. LAMs released transforming growth factor β1 (TGF-β1), which promoted the loss of brown adipocyte identity through aldehyde dehydrogenase 1 family member A1 (Aldh1a1) induction. These findings unfold cell dynamic changes in BAT during obesity and identify LAMs as key responders to tissue metabolic stress and drivers of loss of brown adipocyte identity. Competing Interests: Declaration of interests J.R.B. is a member of the Scientific Advisory Board and receives research support from LUCA Sciences, Inc., has consulted for DeciBio within the past 12 months, receives royalties from Springer Nature Group, and is an inventor on pending patent applications related to the treatment of metabolic diseases and immunoassay diagnostics. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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