Effects of hypothyroidism on the metabolism of lipid emulsion models of triacylglycerol-rich lipoproteins in rats

Abstract

Methimazole-treated hypothyroid rats were injected intravenously with triacylglycerol/cholesteryl oleate/cholesterol/phospholipid emulsions designed to model the composition of chylomicrons. Compared with controls, hypothyroidism decreased the clearance rates of emulsion cholesteryl oleate. Clearance of emulsion triolein was affected much less and could be accounted for by residual triolein in remnants, suggesting that triacylglycerol lipolysis by lipoprotein lipase was unaffected by hypothyroidism but that clearance of remnants from plasma was decreased. Assays in vitro showed increased activities of lipoprotein lipase and hepatic lipase in hypothyroid rats. Emulsions were incubated with post-heparin plasma lipoprotein lipase to prepare remnants in vitro. The clearance from plasma of pre-formed remnants was slower after injection into hypothyroid rats than in control rats. Uptake of remnant cholesteryl oleate by the liver was significantly decreased in the hypothyroid rats. Treatment of hypothyroid rats for 7 days with 3,3',5'-tri-iodo-L-thyronine (T3) reversed the inhibition of hepatic remnant uptake and normalized plasma cholesterol. A thyroid hormone analogue with decreased hypermetabolic side-effects, L-94901, attenuated plasma cholesterol and improved but did not normalize remnant clearance. Emulsions incubated with plasma from hypothyroid rats had a decreased ratio of apolipoprotein E/apolipoprotein C compared with control rats or hypothyroid rats treated with T3. The change in the apolipoprotein E/apolipoprotein C ratio probably accounts for the defect in remnant clearance in hypothyroidism.

Effect of L-thyroxine replacement on apolipoprotein B-48 in overt and subclinical hypothyroid patients

“…We have demonstrated that L-T 4 replacement induces a reduction of fasting serum levels of ApoB-48, which is a static marker of chylomicrons and chylomicron patients with hypothyroidism [18], while other investigators showed significantly decreased clearance of chylomicron remnants in hypothyroid rats [19,20]. Weintraub et al reported that postprandial accumulation of chylomicron remnants exists in the hypothyroid state as a way of indicating an absorption disorder of vitamin A [21].…”

Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD

“…Interestingly, no important side effects were reported. Despite those first promising results, research on both molecules was quickly terminated [ 80 , 81 ].…”

Thyroxine Replacement Therapy Enhances Clearance of Chylomicron Remnants in Patients with Hypothyroidism

“…Other investigators (31)(32)(33)(34) showed significantly decreased clearance of CR in hypothyroid rats. The clearance of chylomicrons, however, was undisturbed.…”