Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity

Jonathan R. Brestoff, Craig B. Wilen, John R. Moley, Yongjia Li, Wei Zou, Nicole P. Malvin, Marina N. Rowen, Brian T. Saunders, Hongming Ma, Madison R. Mack, Barry L. Hykes, Dale R. Balce, Anthony Orvedahl, Jesse W. Williams, Nidhi Rohatgi, Xiaoyan Wang, Michael R. McAllaster, Scott A. Handley, Brian S. Kim, John G. DoenchBernd H. Zinselmeyer, Michael S. Diamond, Herbert W. Virgin, Andrew E. Gelman, Steven L. Teitelbaum

Research output: Contribution to journalArticlepeer-review

Abstract

Brestoff et al. show that adipose-tissue-resident macrophages acquire mitochondria from neighboring adipocytes in a heparan-sulfate-dependent process that is impaired in obesity. Genetic disruption of mitochondria uptake by macrophages reduces energy expenditure and exacerbates diet-induced obesity in mice, indicating that intercellular mitochondria transfer to macrophages mediates systemic metabolic homeostasis.

Original languageEnglish (US)
Pages (from-to)270-282.e8
JournalCell Metabolism
Volume33
Issue number2
DOIs
StatePublished - Feb 2 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) R01-DK111389 , NIH Merit award R37-AR046523 , Shriner’s Hospital for Children grant # 85400 , and a grant from Siteman Cancer Center to S.L.T. Additional funding was provided by the NIH Director’s Early Independence Award ( DP5 OD028125 ), the Burroughs Wellcome Fund (CAMS 1019648 ), and Children’s Discovery Institute ( MI-F-2019-795 ) to J.R.B. Support was also provided by NIH R01-AI123348 (M.S.D.), U19-AI142784 (H.W.V.), K08-AR065577 (B.S.K.), R01-AR070116 (B.S.K.), Doris Duke Charitable Foundation (B.S.K.), Celgene Corporation (B.S.K.), Leo Pharma (B.S.K.), and K99-HL138163 (J.W.W.). The Genome Technology Access Center (GTAC) is partially supported by NCI Cancer Center Support grant P30 CA91842 to Siteman Cancer Center, ICTS/CTSA grant# UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. We thank D. Brinja and E. Lantelme at the flow cytometry and cell sorting Core and E. Tycksen at GTAC at Washington University School of Medicine for their technical support.

Funding Information:
This work was supported by National Institutes of Health (NIH) R01-DK111389, NIH Merit award R37-AR046523, Shriner's Hospital for Children grant #85400, and a grant from Siteman Cancer Center to S.L.T. Additional funding was provided by the NIH Director's Early Independence Award (DP5 OD028125), the Burroughs Wellcome Fund (CAMS 1019648), and Children's Discovery Institute (MI-F-2019-795) to J.R.B. Support was also provided by NIH R01-AI123348 (M.S.D.), U19-AI142784 (H.W.V.), K08-AR065577 (B.S.K.), R01-AR070116 (B.S.K.), Doris Duke Charitable Foundation (B.S.K.), Celgene Corporation (B.S.K.), Leo Pharma (B.S.K.), and K99-HL138163 (J.W.W.). The Genome Technology Access Center (GTAC) is partially supported by NCI Cancer Center Support grant P30 CA91842 to Siteman Cancer Center, ICTS/CTSA grant# UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. We thank D. Brinja and E. Lantelme at the flow cytometry and cell sorting Core and E. Tycksen at GTAC at Washington University School of Medicine for their technical support. J.R.B. C.B.W. J.R.M. M.N.R. N.P.M. Y.L. W.Z. H.M. B.T.S. M.R.M. B.L.S. D.R.B. A.O. and J.W.W. performed experiments. J.R.B. C.B.W. J.R.M. H.M. D.B. A.O. B.H.Z. S.A.H. B.S.K. J.D. G.J.R. M.S.D. H.W.V. A.E.G. and S.L.T. designed the project. J.R.B. C.B.W. J.R.M. Y.L. B.T.S. M.R.M. B.L.H. Jr. W.Z. N.R. X.W. B.H.Z. and J.W.W. analyzed the data. J.R.B. wrote the paper. All authors read, edited, and approved the manuscript. D.R.B. and H.W.V. are employees of J. Virol. Biotechnol. a for-profit institution. H.W.V. is a founder of PierenianDx and Casma Therapeutics. M.S.D. is a consultant for Inbios and on the Scientific Advisory Board of Moderna. B.S.K. has served as a consultant for AbbVie, Inc. Concert Pharmaceuticals, Incyte Corporation, Menlo Therapeutics, and Pfizer, Inc; has participated on the advisory board for Celgene Corporation, Kiniksa Pharmaceuticals, Menlo Therapeutics, Regeneron Pharmaceuticals, Inc. Sanofi, and Theravance Pharmaceuticals; is a stockholder of Gilead Sciences, Inc. and Mallinckrodt Pharmaceuticals; and is a Founder and Chief Scientific Officer of Nuogen Pharma, Inc. The other authors declare no competing interests.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • beige adipose tissue
  • brown adipose tissue
  • horizontal mitochondria transfer
  • immunometabolism
  • intercellular mitochondria transfer
  • macrophage
  • metabolism
  • mitochondria
  • obesity
  • white adipose tissue

PubMed: MeSH publication types

  • Journal Article

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