Bone marrow adipocytes drive the development of tissue invasive Ly6C high monocytes during obesity

Summary 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 Ly6C high monocytes. As BM adiposity also accrues with HFD, we explored the relationship between the gains in BM white adipocytes and invasive Ly6C high monocytes in vivo and through ex vivo paradigms. We find a temporal and causal link between BM adipocyte whitening and the Ly6C high monocyte surge, preceding the adipose tissue macrophage rise during HFD. Phenocopying this, ex vivo treatment of BM cells with conditioned media from BM adipocytes or from bona fide white adipocytes favoured Ly6C high monocyte preponderance. Notably, the switch towards the Ly6C high subset 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 Ly6C high monocytes.