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

Abstract

Interactions between tissues and cell types, mediated by cytokines or direct cell-cell exchanges, regulate growth. To determine whether mature adipocytes influence the in vitro development of trout mononucleated muscle cells, we developed an indirect coculture system, and showed that adipocytes (5x106 cells/well) derived from perivisceral adipose tissue increased the proliferation (BrdU+) of the mononucleated muscle cells (26% versus 39%; P<0.001) while inhibiting myogenic differentiation (myosin+) (25% versus 15%; P<0.001). Similar effects were obtained with subcutaneous adipose tissue-derived adipocytes, although requiring more adipocytes (3x107 cells/well versus 5x106 cells/well). Conditioned media recapitulated these effects, stimulating proliferation (31% versus 39%; p<0.001) and inhibiting myogenic differentiation (32% versus 23%; p<0.001). Adipocytes began to reduce differentiation after 24 hours, whereas proliferation stimulation was observed after 48 hours. While adipocytes did not change pax7+ and myoD1/2+ percentages, they reduced myogenin+ cells showing inhibition from early differentiation stage. Finally, adipocytes increased BrdU+ cells in the Pdgfr+ population but not in the myoD+ one. Collectively, our results demonstrate that trout adipocytes promote fibro-adipocyte precursor proliferation while inhibiting myogenic cells differentiation in vitro, suggesting the key role of adipose tissue in regulating fish muscle growth.