Inhibition of nuclear T3 binding by fatty acids.
Studies were performed to evaluate a possible modulatory role of lipids on the binding of T3 to rat liver nuclear receptors in vitro. Unsaturated fatty acids were potent inhibitors of the binding of [125I] T3 to isolated rat liver nuclei. Doses (in mumol/L) causing a 50% inhibition of nuclear T3 binding were 10 for palmitoleic acid, 11 for linoleic acid, 22 for oleic acid, 24 for arachidonic acid, and 37 for linolenic acid. Other lipids had less or no inhibitory activity. Unsaturated fatty acids reduced the affinity constant (Ka) of the binding of T3 to nuclear receptors to 57.4% +/- 11.0% that of controls (mean +/- SE 1.04 +/- 0.14 v 1.97 +/- 0.23 10(9) L/M, n = 5; P less than .02) but did not affect the maximal binding capacity (MBC) (1.47 +/- 0.20 v 1.55 +/- 0.10 10(-10) M/L; NS). Evaporated ether extracts of rat liver homogenate pretreated with phospholipase A2 for five to 20 minutes (that liberates unsaturated fatty acids from phospholipids) demonstrated a progressive inhibition of nuclear T3 binding with time when compared with ether extracts of untreated rat liver homogenate (F = 16.1; P less than .01). Evaporated, fatty-acid-rich ether extracts of human sera caused a dose-dependent inhibition in the binding of [125I] T3 to nuclear T3 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Wiersinga
W M
WM
Department of Medicine, UCLA Center for the Health Sciences 90024.
Chopra
I J
IJ
Teco
G N
GN
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D002784:Cholesterol; D013974:Thyroxine