Bone marrow adipocytes drive the development of tissue invasive Ly6Chigh monocytes during obesity
Parastoo Boroumand,
David C Prescott,
Tapas Mukherjee,
Philip J Bilan,
Michael Wong,
Jeff Shen,
Ivan Tattoli,
Yuhuan Zhou,
Angela Li,
Tharini Sivasubramaniyam,
Nancy Shi,
Lucie Y Zhu,
Zhi Liu,
Clinton Robbins,
Dana J Philpott,
Stephen E Girardin,
Amira Klip
Affiliations
Parastoo Boroumand
Cell Biology Program, The Hospital for Sick Children, Toronto, Canada; Department of Biochemistry, University of Toronto, Toronto, Canada
David C Prescott
Department of Immunology, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathophysiology, University of Toronto, Toronto, Canada
Tapas Mukherjee
Department of Immunology, University of Toronto, Toronto, Canada
Philip J Bilan
Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
Michael Wong
Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
Jeff Shen
Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
Ivan Tattoli
Department of Laboratory Medicine and Pathophysiology, University of Toronto, Toronto, Canada
Yuhuan Zhou
Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
Angela Li
Toronto General Hospital Research Institute, Toronto, Canada
Tharini Sivasubramaniyam
Toronto General Hospital Research Institute, Toronto, Canada
Nancy Shi
Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
Zhi Liu
Cell Biology Program, The Hospital for Sick Children, Toronto, Canada
Clinton Robbins
Department of Laboratory Medicine and Pathophysiology, University of Toronto, Toronto, Canada; Toronto General Hospital Research Institute, Toronto, Canada
Dana J Philpott
Department of Immunology, University of Toronto, Toronto, Canada
Stephen E Girardin
Department of Immunology, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathophysiology, University of Toronto, Toronto, Canada
During obesity and high fat-diet (HFD) feeding in mice, sustained low-grade inflammation includes not only increased pro-inflammatory macrophages in the expanding adipose tissue, but also bone marrow (BM) production of invasive Ly6Chigh monocytes. As BM adiposity also accrues with HFD, we explored the relationship between the gains in BM white adipocytes and invasive Ly6Chigh monocytes by in vivo and ex vivo paradigms. We find a temporal and causal link between BM adipocyte whitening and the Ly6Chigh monocyte surge, preceding the adipose tissue macrophage rise during HFD in mice. Phenocopying this, ex vivo treatment of BM cells with conditioned media from BM adipocytes or bona fide white adipocytes favoured Ly6Chigh monocyte preponderance. Notably, Ly6Chigh skewing was preceded by monocyte metabolic reprogramming towards glycolysis, reduced oxidative potential and increased mitochondrial fission. In sum, short-term HFD changes BM cellularity, resulting in local adipocyte whitening driving a gradual increase and activation of invasive Ly6Chigh monocytes.
