Lipid-associated macrophages reshape BAT cell identity in obesity

Francesca Sciarretta; Andrea Ninni; Fabio Zaccaria; Valerio Chiurchiù; Adeline Bertola; Keaton Karlinsey; Wentong Jia; Veronica Ceci; Claudia Di Biagio; Ziyan Xu; Francesco Gaudioso; Flavia Tortolici; Marta Tiberi; Jiabi Zhang; Simone Carotti; Sihem Boudina; Paolo Grumati; Beiyan Zhou; Jonathan R. Brestoff; Stoyan Ivanov; Katia Aquilano; Daniele Lettieri-Barbato

doi:10.1016/j.celrep.2024.114447

Lipid-associated macrophages reshape BAT cell identity in obesity

Francesca Sciarretta, Andrea Ninni, Fabio Zaccaria, Valerio Chiurchiù, Adeline Bertola, Keaton Karlinsey, Wentong Jia, Veronica Ceci, Claudia Di Biagio, Ziyan Xu, Francesco Gaudioso, Flavia Tortolici, Marta Tiberi, Jiabi Zhang, Simone Carotti, Sihem Boudina, Paolo Grumati, Beiyan Zhou, Jonathan R. Brestoff, Stoyan IvanovKatia Aquilano, Daniele Lettieri-Barbato

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	114447
Journal	Cell Reports
Volume	43
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2024.114447
State	Published - Jul 23 2024

Keywords

CP: Metabolism
adipocytes
extracellular mitochondria
immunometabolism
metabolism
mitochondria
single-cell RNA sequencing
thermogenesis
type 2 diabetes

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10.1016/j.celrep.2024.114447

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Sciarretta, F., Ninni, A., Zaccaria, F., Chiurchiù, V., Bertola, A., Karlinsey, K., Jia, W., Ceci, V., Di Biagio, C., Xu, Z., Gaudioso, F., Tortolici, F., Tiberi, M., Zhang, J., Carotti, S., Boudina, S., Grumati, P., Zhou, B., Brestoff, J. R., ... Lettieri-Barbato, D. (2024). Lipid-associated macrophages reshape BAT cell identity in obesity. Cell Reports, 43(7), Article 114447. https://doi.org/10.1016/j.celrep.2024.114447

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title = "Lipid-associated macrophages reshape BAT cell identity in obesity",

abstract = "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.",

keywords = "CP: Metabolism, adipocytes, extracellular mitochondria, immunometabolism, metabolism, mitochondria, single-cell RNA sequencing, thermogenesis, type 2 diabetes",

author = "Francesca Sciarretta and Andrea Ninni and Fabio Zaccaria and Valerio Chiurchi{\`u} and Adeline Bertola and Keaton Karlinsey and Wentong Jia and Veronica Ceci and {Di Biagio}, Claudia and Ziyan Xu and Francesco Gaudioso and Flavia Tortolici and Marta Tiberi and Jiabi Zhang and Simone Carotti and Sihem Boudina and Paolo Grumati and Beiyan Zhou and Brestoff, {Jonathan R.} and Stoyan Ivanov and Katia Aquilano and Daniele Lettieri-Barbato",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = jul,

day = "23",

doi = "10.1016/j.celrep.2024.114447",

language = "English",

volume = "43",

journal = "Cell Reports",

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Sciarretta, F, Ninni, A, Zaccaria, F, Chiurchiù, V, Bertola, A, Karlinsey, K, Jia, W, Ceci, V, Di Biagio, C, Xu, Z, Gaudioso, F, Tortolici, F, Tiberi, M, Zhang, J, Carotti, S, Boudina, S, Grumati, P, Zhou, B, Brestoff, JR, Ivanov, S, Aquilano, K & Lettieri-Barbato, D 2024, 'Lipid-associated macrophages reshape BAT cell identity in obesity', Cell Reports, vol. 43, no. 7, 114447. https://doi.org/10.1016/j.celrep.2024.114447

TY - JOUR

T1 - Lipid-associated macrophages reshape BAT cell identity in obesity

AU - Sciarretta, Francesca

AU - Ninni, Andrea

AU - Zaccaria, Fabio

AU - Chiurchiù, Valerio

AU - Bertola, Adeline

AU - Karlinsey, Keaton

AU - Jia, Wentong

AU - Ceci, Veronica

AU - Di Biagio, Claudia

AU - Xu, Ziyan

AU - Gaudioso, Francesco

AU - Tortolici, Flavia

AU - Tiberi, Marta

AU - Zhang, Jiabi

AU - Carotti, Simone

AU - Boudina, Sihem

AU - Grumati, Paolo

AU - Zhou, Beiyan

AU - Brestoff, Jonathan R.

AU - Ivanov, Stoyan

AU - Aquilano, Katia

AU - Lettieri-Barbato, Daniele

PY - 2024/7/23

Y1 - 2024/7/23

N2 - 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.

AB - 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.

KW - CP: Metabolism

KW - adipocytes

KW - extracellular mitochondria

KW - immunometabolism

KW - metabolism

KW - mitochondria

KW - single-cell RNA sequencing

KW - thermogenesis

KW - type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85197286074&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2024.114447

DO - 10.1016/j.celrep.2024.114447

M3 - Article

C2 - 38963761

AN - SCOPUS:85197286074

SN - 2211-1247

VL - 43

JO - Cell Reports

JF - Cell Reports

IS - 7

M1 - 114447

ER -

Lipid-associated macrophages reshape BAT cell identity in obesity

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Keywords

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