Hypothyroidism and thyroxin substitution affect the n−3 fatty acid composition of rat liver mitochondria

Abstract

The effects of hypothyroidism and of daily treatment for up to 21 days with thyroxin (T4, 0.5 micrograms/100 g body weight) on the fatty acid composition of total lipid, phosphatidylethanolamine, and phosphatidylcholine of rat liver mitochondria were studied. The fatty acid compositions of hypothyroid and euthyroid (control) rats of similar age were compared. The n-6 and n-3 polyunsaturated fatty acids (PUFA) were affected differently by the hypothyroid state. The levels of linoleic (18:2n-6), gamma-linolenic (18:3n-6) and dihomo-gamma-linolenic acids (20:3n-6) were higher in hypothyroid rats than in controls, while the level of arachidonic acid (20:4n-6) was lower, which suggests an impairment of the elongase and desaturase activities. The n-3 polyunsaturated fatty acids, eicosapentaenoic (EPA, 20:5n-3) and docosapentaenoic (22:5n-3) acids, were higher in hypothyroid rats, whereas the linolenic acid (18:3n-3) content remained constant. The level of docosahexaenoic acid (DHA, 22:6n-3) was dramatically decreased in hypothyroid rats, while the levels of C22 n-6 fatty acids were unchanged. The differences were probably due to the competition between n-3 and n-6 PUFA for desaturases, elongases and acyltransferases. When hypothyroid rats were treated with thyroxin, the changes induced by hypothyroidism in the proportions of n-6 fatty acids were rapidly reversed, while the changes in the n-3 fatty acids were only partially reversed. After 21 days of thyroxin treatments, the DHA content was only half as high in hypothyroid rats than in euthyroid rats. These results suggest that the conversion of 18:2n-6 to 20:4n-6 is suppressed in the hypothyroid state which favors the transformation of 18:3n-3 to 20:5n-3.(ABSTRACT TRUNCATED AT 250 WORDS)