Fatty acid inhibition of sulfation factor-stimulated 35 SO 4 incorporation into embryonic chicken cartilage.

The effect of fatty acids and ketones on 35S04 incorporation into the chondromucoproteins of embryonic chicken cartilage was studied in vitro. Both the nonstimulated incorporation (that occurring in media without added serum) and sulfation factor stimulated incorporation (that occurring in media with 5.0% rat serum added) were investigated. Butyrate and octanoate, from 0.01 mM to 1.0 mu, had minimal effects on nonstimulated 35S04 incorporation. At 5.0 mM both caused moderate inhibition of Y’304 incorporation into the cartilage. In the serum stimulated state, butyrate and octanoate, at 0.5 mM, 1.0 mM, and 5.0 mM, resulted in striking dose-related inhibition of 35S04 incorporation. Palmitate and oleate from 0.1 mM to 1.0 mM had no effect on nonstimulated 35S04 incorporation, but did cause marked inhibition of the serum-stimulated component of 35S04 incorporation. P-Hydroxybutyrate, acetoacetate, and acetate, from 0.1 mu to 5.0 mu, had no effect on either nonstimulated or serum-stimulated 35S04 incorpdration. 35S04 incorporation into cartilage chondromucoproteins was independent of glucose over a concentration range of 2.5 mM to 15.0 mM. In the absence of glucose in the medium, nonstimulated W04 incorporation was markedly inhibited, but the incremental increase stimulated by rat serum was unaffected. The inhibitory effect of butyrate on serum-stimulated 35S04 incorporation is reversible and this indicates that the fatty acid effect is not a nonspecific toxic action. The data suggest that fatty acids may regulate the synthesis of chondromucoproteins in cartilage and in this way dissociate the lipolytic and glucose mobilizing effects of growth hormone from its stimulation of growth. Though the locus of action of fatty acids on W04 incorporation is unknown, it may be at the site of the action of sulfation factor.