Δ6 and Δ5 desaturase activities in liver from obese zucker rats at different ages

Δ6 Desaturation of linoleic acid (18∶2 n−6) and Δ5 desaturation of dihomo-γ-linolenic acid (20∶3 n−6) were measured in liver microsomes from genetically obese Zucker rats (fa/fa) and from their lean littermates (Fa/−). Both groups were fed a balanced commercial diet. The rats were 6, 9 and 12 weeks old, which corresponded to stages in their active growth period. The content of total fatty acids and n−6 polyunsaturated fatty acids in whole liver and liver microsomes was also determined in order to ascertain how the desaturase activities measuredin vitro reflected regulation of essential fatty acid metabolismin vivo. Contrary to values obtained for Δ6 desaturation, Δ5 desaturation at nonsaturating substrate levels were lower in obese rats than in lean controls. In contrast, at saturating substrate level, the maximal Δ5 desaturase activities were the same in both phenotypes and they increased with age. Study of Δ5 desaturation kinetics (1/V vs 1/S) showed that V_m did not differ between 12-week-old obese and lean rats, whereas K_M in obese rats was much lower than in controls, expressing the very low affinity of the enzyme for the substrate in obese animals. The fatty acid composition of liver lipids reflected the results of desaturase activitiesin vitro. In particular, the ratios 20∶4 n−6/20∶3 n−6 were lower in obese rats than in lean rats, which can be explained by the lower conversion of 20∶3 n−6 into 20∶4 n−6 by Δ5 desaturation. However, the total amount of 20∶4 n−6 in the whole liver did not differ between phenotypes, whatever their age. This work presents evidence for a relationship between the changes in fatty acid compositional data in hepatic total lipids, total lipids of liver microsomes and modifications of fatty acid desaturase activities in the genetically obese Zucker rat.