THE DECREASE OF LIVER LDL RECEPTOR MESSENGER-RNA DURING FASTING IS RELATED TO THE DECREASE IN SERUM T3

Fasting is associated with a reduction in serum T3 and T4 and a rise o f plasma LDL cholesterol. We hypothesized that an hypothyroid-like con dition induced by fasting is responsible for the rise in LDL cholester ol. We therefore examined the relation between changes in thyroid horm one and cholesterol metabolism in rats fasted for 0, 8, 12, 24 or 48 h . Fasting resulted in a decrease of liver 5'-deiodinase mRNA from 8 h (to 50%, p < 0.05, n = 6), of serum T3 from 12 h and of serum T4 at 48 h; serum TSH remained unchanged. Furthermore, plasma LDL cholesterol increased from 24 h onwards preceded by a decrease of liver LDL recept or mRNA which in turn is related to serum T3 (r = 0.55, p < 0.05, n = 19). Adding T3 at a concentration such that normal T3 levels are maint ained during 48 h fasting, prevents the decrease in the LDL receptor m RNA. Fasting did not change hepatic HMG CoA reductase mRNA but decreas ed cholesterol 7 alpha-hydroxylase mRNA, which however was not related to the decrease of serum T3. In conclusion: (I) Fasting induces a hyp othyroid-like condition in which inhibition of hepatic conversion of T 4 into T3 may be responsible for the decrease of serum T3. (2) Fasting induces an increase of plasma LDL cholesterol, apparently caused by a decrease of hepatic LDL receptor gene expression which is (partly) re lated to the fall in serum T3. (234). (C) 1998 Elsevier Science Ltd. A ll rights reserved.