Role of mast cells in age-related brown adipocyte dysfunction

Einleitung:

The cellular microenvironment strongly influences the differentiation capacity of progenitor cells that give rise to brown adipocytes. The extracellular matrix is an important component of the microenvironment serving as a scaffold for adipogenesis. Furthermore, other cell types may influence the development of brown adipocytes. It is well-established that immune cells can act as regulatory elements of adipocyte function. We show that brown adipose tissue (BAT)-resident mast cells, which secrete small molecules like histamine, heparin and specific matrix-modulating proteases, may contribute to the age-related changes in the microenvironment impairing brown adipogenesis.

Methoden:

RNAseq analysis of BAT and proteome analysis of whole and decellularized BAT from young and aged mice was conducted using a mass spectrometry-based approach. To evaluate differences in the microenvironment that may affect brown adipogenesis, effects of mast cells on brown adipocytes were investigated using co-culture assays.

Ergebnisse:

Aging affects brown adipose tissue microenvironment and the resident progenitor cells by influencing ECM turnover and mast cell activity. The number of BAT-residing mast cells is increased age-dependently. Moreover, exposure of progenitors to mast cell-derived factors impairs brown adipogenesis.

Schlussfolgerung:

Taken together, the negative effect of mast cells on brown adipogenesis may exacerbate metabolic pathologies, such as insulin resistance and obesity with increased age.