Control of terminal differentiation of adipose precursor cells by glucocorticoids.
The role of glucocorticoids on adipose conversion has been studied using confluent Ob1771 mouse preadipose cells maintained in a serum-free culture medium able to support the emergence of early but not that of late markers of differentiation. Under these culture conditions, glucocorticoids play, at physiological concentrations, a permissive role for terminal differentiation, characterized by glycerol-3-phosphate dehydrogenase expression and triacylglycerol accumulation within 12 days, whereas progesterone, testosterone, and estradiol are inactive. Glucocorticoids behave as mitogenic-adipogenic stimuli able to trigger growth-arrested, early marker-expressing cells to enter the terminal phase of the differentiation program and thus appear to mimic the mitogenic-adipogenic activity already described for arachidonic acid and cyclic AMP-elevating agents, especially prostacyclin. When compared to corticosterone alone, exposure of Ob1771 cells to both corticosterone and arachidonic acid leads to an additional increase in the glycerol-3-phosphate dehydrogenase activity and number of differentiated cells; this potentiation is further enhanced when the culture medium is supplemented with the cyclic AMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. This suggests indirectly the involvement of prostacyclin as a metabolite of arachidonic acid able to induce cyclic AMP accumulation. In agreement with this hypothesis, it is found that a promoting effect is exerted by corticosterone on the metabolism of arachidonic acid, leading in turn to an increase in the production of prostacyclin. These findings allow a better understanding of the role of glucocorticoids on adipose cell differentiation and explain a posteriori the effectiveness of the combination of dexamethasone-isobutyl-methylxanthine used in innumerable studies.
Gaillard
D
D
Centre de Biochimie du CNRS (UPR 7300), UFR Sciences, Nice, France.
Wabitsch
M
M
Pipy
B
B
Négrel
R
R
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003345:Corticosterone / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008934:Mitogens / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D001095:Arachidonic Acids; D005938:Glucocorticoids; D008934:Mitogens; D000242:Cyclic AMP; D003345:Corticosterone