Changes in the metabolism of long chain fatty acids during adipose differentiation of 3T3 L1 cells.

A study was made of the kinetics of utilization of [9,10-3H]palmitate by 3T3 L1 cells undergoing slow spontaneous adipose differentiation and by a population of 3T3 L1 cells treated with 1-methylisobutylxanthine (MIX) and dexamethasone (DEX) to accelerate adipose differentiation. The results showed that, early in the course of the induced differentiation, the specific rate of beta-oxidation of long chain fatty acids (kappa 1) fell precipitously, particularly during the 2 days of exposure of the cells to MIX + DEX. The value of kappa 1 decreased slowly with the passage of time in untreated cells, a small proportion of which differentiated to adipocytes. In MIX + DEX-treated cells the abrupt decline in the rate of fatty acid oxidation was followed by a decrease in the rate of carnitine uptake. Both changes preceded the appearance of detectable alpha-glycerophosphate dehydrogenase activity, a sensitive indicator of adipose differentiation, and came well before the appearance of lipid droplets. Esterification was found to be the principal route of fatty acid utilization both by preadipocytes and by cells committed to adipose differentiation. With the passage of time, the specific rate of fatty acid esterification (kappa 2) increased by two-thirds in untreated cells but in the same period more than doubled in MIX + DEX-treated cells. Thus, while the ratio of kappa 2/kappa 1 rose in 9 days to 7.6 in untreated cells, it increased to 28.3 in treated cells. Measurements of the rate of lipolysis (kappa 3) showed no significant difference between preadipocytes and cells committed to adipose differentiation.