Inhibition of rat perirenal preadipocyte differentiation

The process of adipose differentiation uniquely endows fat cells to accrue triacylglycerols under conditions of nutrient energy surfeit and to release fatty acids during energy deprivation. The object of this investigation was to study influences on this process in perirenal preadipocytes, grown in primary culture or first subculture and derived from male Sprague-Dawley rats, 180-200 g. Supplementation of the culture medium with 1-methyl-3-isobutylxanthine, corticosterone, and insulin induced differentiation in practically all perirenal preadipocytes, as indicated morphologically and by rising glycerophosphate dehydrogenase activity. Appreciable differentiation was induced even in the absence of methylisobutylxanthine. Transforming growth factor beta (1-1000 pM), cachectin (tumour necrosis factor alpha) (1-1000 pM), and basic fibroblast growth factor (0.063-63 nM) inhibited adipose differentiation significantly, almost completely at the higher concentrations. Direct inhibition, rather than a persisting mitogenic effect of fibroblast growth factor, was confirmed using demecolcine (Colcemid). The fact that transforming growth factor beta and cachectin inhibit differentiation in preadipocytes from postpubertal rats suggests that this effect probably also occurs in vivo, thus diverting energy from adipose depots in certain neoplastic and inflammatory states. We propose that the anterior pituitary, through fibroblast growth factor(s), modulates the pool of preadipocytes and other mesenchymal cells. The mitogenic effect would be complemented by a concerted function, inhibition of adipose differentiation, resulting in the retention of a greater number of potentially replicative cells. Then, depending on the subject's nutritional and endocrine status, extrapituitary factors would regulate the specific process of differentiation.