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Hepatic lipogenesis and cholesterol synthesis in hyperthyroid patients.
A Cachefo1, P Boucher, C Vidon
1INSERM, U-499, and Genalys, Université R. T. H. Laennec, Laboratoire de Biochimie, Hôpital E. Herriot, Centre de Recherche en Nutrition Humaine, Hôpital E. Herriot, 69008 Lyon, France.
The Journal of Clinical Endocrinology and Metabolism
|November 10, 2001
Summary
Hyperthyroidism significantly boosts hepatic lipogenesis and cholesterol synthesis, leading to higher triglycerides but lower plasma cholesterol due to increased clearance. This impacts metabolic pathways in thyroid patients.
Area of Science:
- Endocrinology and Metabolism
- Molecular Biology
Background:
- Thyroid hormones profoundly influence metabolic processes.
- Hyperthyroidism is associated with altered lipid profiles, but its specific effects on hepatic lipogenesis and cholesterol synthesis require detailed investigation.
Purpose of the Study:
- To elucidate the impact of hyperthyroidism on hepatic lipogenesis and cholesterol synthesis.
- To investigate the underlying molecular mechanisms, including gene expression, in hyperthyroid individuals.
Main Methods:
- Utilized the deuterated water method to measure metabolic pathways in postabsorptive euthyroid and hyperthyroid subjects.
- Quantified plasma metabolites, including glucose, insulin, nonesterified fatty acids, triglycerides, and cholesterol.
- Assessed mRNA levels of key enzymes and receptors (HMGCR, LDL receptor, LRP) in circulating mononuclear cells.
Main Results:
- Hyperthyroid patients exhibited increased glucose, insulin, nonesterified fatty acids, and triglycerides, with decreased plasma cholesterol.
- Hepatic lipogenesis contribution to plasma triglycerides was significantly elevated (23.0% vs 7.5%) in hyperthyroid subjects.
- Cholesterol fractional synthetic rate was moderately increased (5.0% vs 3.3%), and HMGCR mRNA levels were higher, while LDL receptor and LRP mRNA levels remained unchanged.
Conclusions:
- Hyperthyroidism markedly stimulates hepatic lipogenesis, likely due to direct thyroid hormone action and increased insulin levels, contributing to elevated triglycerides.
- The observed decrease in plasma cholesterol, despite enhanced synthesis, suggests an increased clearance rate, potentially involving non-LDL receptors.
- Gene expression data indicates a complex regulation of lipid metabolism in hyperthyroidism.