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.
