Secretion of nascent lipoproteins by isolated hepatocytes from hypothyroid and hypothyroid, hypercholesterolemic rats.
The induction of hypothyroidism in the rat is necessary for the development of pronounced dietary-induced hypercholesterolemia. The nature of nascent lipoproteins secreted by isolated hepatocytes from euthyroid, hypothyroid and hypothyroid, cholesterol-fed rats was investigated to distinguish between these hormonal and dietary effects. Serum total lipids, apolipoproteins, B, E and A-I, were greatly elevated in hypercholesterolemia. In hypothyroidism, serum apolipoproteins B and E were elevated, triacylglycerols were reduced by 65% and free cholesterol was increased by 50%. The total lipid, apolipoprotein B and E, secreted by hypercholesterolemic rat hepatocytes was markedly elevated when compared to normal. Triacylglycerol and phospholipid secretion was slightly increased by hypothyroid rat hepatocytes; however, apolipoprotein B, E and A-I secretion rates were unaffected. Gel filtration of the nascent lipoproteins demonstrated that compared to normal, proportionately more apolipoprotein B and E from hypercholesterolemic rat hepatocytes and apolipoprotein E from hypothyroid rat hepatocytes was secreted as larger lipoproteins. Hypercholesterolemic rat hepatocytes secreted abnormal cholesterol-rich particles even after 24 h of incubation in a lipid-deficient medium. Hypothyroidism alone cannot account for this observation, as hypothyroid rat hepatocytes secreted a triacylglycerol-rich, cholesterol-deficient lipoprotein having a normal nascent lipoprotein lipid composition. These observations are consistent with the hypothesis that in hypothyroidism the accumulation of beta-migrating lipoproteins results from impaired removal of lipoprotein catabolites from the serum, a condition which would only promote hypercholesterolemia in cholesterol feeding where direct synthesis of abnormal lipoproteins occurs.
D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism*; D007037:Hypothyroidism / Q000150:complications / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000097:blood; D011441:Propylthiouracil; D051381:Rats; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D002788:Cholesterol Esters; D008074:Lipoproteins; D010743:Phospholipids; D014280:Triglycerides; D011441:Propylthiouracil; D002784:Cholesterol