Mitochondrial metabolism is a key regulator of the fibro-inflammatory and adipogenic stromal subpopulations in white adipose tissue

The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their behaviors in response to stimuli, such as overfeeding, however, are unclear. Here, we show that the developmental fates and functional properties of adipose platelet-derived growth factor receptor beta (PDGFRβ)+ progenitor subpopulations are tightly regulated by mitochondrial metabolism. Reducing the mitochondrial β-oxidative capacity of PDGFRβ+ cells via inducible expression of MitoNEET drives a pro-inflammatory phenotype in adipose progenitors and alters lineage commitment. Furthermore, disrupting mitochondrial function in PDGFRβ+ cells rapidly induces alterations in immune cell composition in lean mice and impacts expansion of adipose tissue in diet-induced obesity. The adverse effects on adipose tissue remodeling can be reversed by restoring mitochondrial activity in progenitors, suggesting therapeutic potential for targeting energy metabolism in these cells. [Display omitted] •Adipogenic and inflammatory precursors have distinct metabolic properties•Mitochondrial activity is crucial for precursors to differentiate into mature adipocytes•Mitochondrial dysfunction promotes inflammatory characteristics of mural cells•Maintenance of mural identity requires proper mitochondrial function Factors controlling the degree of lineage commitment of PDGFRβ+ subpopulations are poorly defined. Here, Joffin et al. demonstrate that mitochondrial activity determines the cellular identity of adipocyte precursors and lineage commitment and pinpoint PdgfRβ+ cells as key regulators of inflammation and adipose tissue remodeling during caloric excess.