Mature adipocytes inhibit differentiation of myogenic cells but stimulate proliferation of fibro-adipogenic precursors derived from trout musclein vitro

Abstract

AbstractInteractions between tissues and cell types, mediated by cytokines or direct cell-cell exchanges, regulate growth. To determine whether mature adipocytes influence thein vitrodevelopment of trout mononucleated muscle cells, we developed an indirect coculture system, and showed that adipocytes (5×106cells/well) derived from perivisceral adipose tissue increased the proliferation (BrdU+) of the mononucleated muscle cells (26%versus39%; P<0.001) while inhibiting myogenic differentiation (myosin+) (25%versus15%; P<0.001). Similar effects were obtained with subcutaneous adipose tissue-derived adipocytes, although requiring more adipocytes (3×107cells/wellversus5×106cells/well). Conditioned media recapitulated these effects, stimulating proliferation (31%versus39%; p<0.001) and inhibiting myogenic differentiation (32%versus23%; p<0.001). Adipocytes began to reduce differentiation after 24 hours, whereas proliferation stimulation was observed after 48 hours. While adipocytes did not changepax7+andmyoD1/2+percentages, they reducedmyogenin+cells showing inhibition from early differentiation stage. Finally, adipocytes increased BrdU+cells in thePdgfrα+population but not in themyoD+one. Collectively, our results demonstrate that trout adipocytes promote fibro-adipocyte precursor proliferation while inhibiting myogenic cells differentiationin vitro, suggesting the key role of adipose tissue in regulating fish muscle growth.