Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states.
This article reviews our understanding of effects of thyroid hormone excess and deficiency on hepatic metabolism of FFA, and consequent effects on production, secretion, and metabolism of plasma lipoproteins. In the hyperthyroid state the following alterations are observed. Fatty acid oxidation and ketogenesis are stimulated simultaneously with a paradoxical stimulation of fatty acid synthesis, which may be linked by virtue of a blunted response of mitochondrial carnitine palmitoyltransferase I (CPT-I) to malonyl coenzyme A (CoA). Esterification of fatty acid to triglyceride (TG) is reduced, as is the secretion of the very low density lipoprotein (VLDL) (including VLDL TG, cholesterol, and apoprotein); this may be due, in part, to decreased concentrations of glycerol-3-phosphate (G3P) in the hepatic cell. In the intact animal or patient, however, serum TG concentration is variable, which may reflect increased adipose tissue lipolysis and elevated concentrations of plasma FFA, which would tend to drive VLDL secretion by the liver. Clearance of the VLDL and its metabolic product, the low density lipoprotein (LDL), is increased, resulting in decreased plasma total and LDL cholesterol. Although high density lipoprotein (HDL) cholesterol may also be reduced, the ratio of LDL/HDL cholesterol is further decreased. The regulatory role of the lipoprotein apoproteins is less clear, but hepatic apolipoprotein (apo) B secretion (required for VLDL) is diminished, while apo-AI secretion (required for HDL) is stimulated, perhaps both reflecting rates of synthesis. Plasma concentrations of apo-AI are variable, dependent on relative rates of secretion and clearance. In the hypothyroid, many of these effects are reversed, which results in hyperlipoproteinemias and greater risk for the development of atherosclerotic cardiovascular disease.
D000409:Alanine / Q000494:pharmacology; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D007657:Ketone Bodies / Q000096:biosynthesis; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008074:Lipoproteins / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000096:biosynthesis; D014284:Triiodothyronine / Q000494:pharmacology
D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D007773:Lactates; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D009829:Oleic Acids; D014280:Triglycerides; D014284:Triiodothyronine; D019301:Oleic Acid; D019344:Lactic Acid; D000409:Alanine