Hepatic Lipogenesis and Cholesterol Synthesis in Hyperthyroid Patients

Abstract

To determine the effect of hyperthyroidism on hepatic lipogenesis and cholesterol synthesis we measured these metabolic pathways (deuterated water method) in euthyroid and hyperthyroid subjects investigated in the postabsorptive state. Hyperthyroid patients had increased concentrations of glucose (P < 0.05), insulin (P < 0.05), nonesterified fatty acids (P < 0.01), and triglycerides (P < 0.05) and decreased levels of plasma cholesterol (P < 0.01). The contribution of hepatic lipogenesis to plasma triglycerides was largely increased in hyperthyroid subjects (23.0 +/- 1.8% vs. 7.5 +/- 0.2%; P < 0.001), whereas the fractional synthetic rate of cholesterol was moderately higher (5.0 +/- 0.8% vs. 3.3 +/- 0.2%; P < 0.05). mRNA levels of beta-hydroxy-beta-methyl glutaryl-coenzyme A reductase, measured in circulating mononuclear cells, were increased (P < 0.05), whereas those of low density lipoprotein (LDL) receptor and LDL receptor-related protein were unchanged. Sterol responsive element binding protein-1c mRNAs were undetectable in mononuclear cells from both groups of subjects. The large stimulation of hepatic lipogenesis in hyperthyroid patients is probably explained by both a direct action of thyroid hormones and the increase in insulin. It could contribute to their moderate rise in triglycerides levels. The decreased plasma cholesterol level is observed despite an enhanced synthetic rate and is thus related to an increased clearance rate. The lack of increased expression of LDL receptor and LDL receptor-related protein suggests that other receptors are implicated.

Mechanisms of the Triglyceride- and Cholesterol-Lowering Effect of Fenofibrate in Hyperlipidemic Type 2 Diabetic Patients

“…However, these mRNAs levels were not measured in hepatocytes but in circulating mononuclear cells. Although this was initially suggested (39), it is unclear whether these cells can be considered as representative of hepatocytes with respect to the expression of key regulatory genes of cholesterol metabolism (19). With respect to the lack of decrease of cholesterol ASR after treatment by fenofibrate, the method used for measuring cholesterol synthesis does not allow the delineation of respective contributions of liver and extra-hepatic tissues to the sampled pool of cholesterol.…”

“…Plasma insulin and glucagon concentrations were determined by radioimmunoassay. Total, unesterified, and HDL cholesterol were measured as previously described (18,19). LDL cholesterol was calculated using the equation of Friedewald, except in subjects with plasma triglycerides Ͼ4.5 mmol/l.…”

“…LDL receptor and hydroxymethylglutaryl (HMG)-CoA reductase mRNA copy numbers were determined by competitive RT-PCR. The detailed procedure has been previously reported (19). The results were expressed as copy number per g of total cellular RNA.…”

Differences in the regulation of adipose tissue and liver lipogenesis by carbohydrates in humans

“…Procedures for the extraction of total RNA and the measurements of mRNA concentrations of FAS, ACC1, and SREBP-1c have been described previously (11,25,26).…”

Stimulation of cholesterol synthesis and hepatic lipogenesis in patients with severe malabsorption

“…LRP mRNA concentrations were measured by RT-competitive PCR. The detailed procedure has been published previously (18,19). The results were expressed as copy number per microgram of total cellular RNA.…”