Related Experiment Video
Updated: Jul 31, 2026
10:59
Production of Apolipoprotein C-III Knockout Rabbits using Zinc Finger Nucleases
Published on: November 19, 2013
Thyroid hormone regulates the hypotriglyceridemic gene APOA5
Xavier Prieur1, Thierry Huby, Hervé Coste
1GlaxoSmithKline, 25 Avenue du Québec, 91951 Les Ulis cedex, France.
The Journal of Biological Chemistry
|June 9, 2005
Summary
Thyroid hormone (T3) directly regulates the APOA5 gene, increasing its expression. This discovery reveals a new mechanism for thyroid hormone in managing triglyceride levels and suggests TRbeta as a potential drug target for hypertriglyceridemia.
Area of Science:
- Molecular Endocrinology
- Lipid Metabolism
- Genetics
Background:
- Apolipoprotein AV (APOA5) is crucial for triglyceride regulation and linked to cardiovascular disease.
- Thyroid hormones influence lipid metabolism, with inverse correlations observed between thyroid status and triglyceride levels.
Purpose of the Study:
- To investigate if thyroid hormone regulates the APOA5 gene.
- To elucidate the molecular mechanisms of this regulation.
Main Methods:
- Hepatocyte cell culture treated with T3 and a TRbeta ligand.
- Reporter assays to assess APOA5 promoter activity.
- Analysis of transcription factor cooperation (USF1/2 with TR).
- In vivo studies in rats with thyroid hormone depletion and T3 administration.
Main Results:
- T3 and a TRbeta ligand significantly increased APOA5 mRNA and protein levels in hepatocytes.
- T3-activated thyroid receptor (TR) directly binds and activates the APOA5 promoter via a DR4 element.
- Upstream stimulatory factors (USF1/2) synergistically enhance T3-induced APOA5 activation via an adjacent E-box.
- In rats, thyroid hormone depletion reduced apoAV levels, which were restored by T3 treatment.
- TRbeta activation increased apoAV and decreased triglyceride levels in vivo.
Conclusions:
- APOA5 is a direct target gene of thyroid hormone.
- Thyroid hormone influences triglyceride homeostasis partly through regulating APOA5.
- TRbeta activation presents a potential therapeutic strategy for hypertriglyceridemia.
Related Concept Videos
01:20Synthesis and Regulation of Thyroid Hormones
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
01:18Functions of Thyroid Hormones
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:23Hypothyroidism II: Pathophysiology
Hypothyroidism is a disorder characterized by insufficient production of thyroid hormones, which regulate metabolism, energy balance, and multiple organ systems.TypesHypothyroidism is classified based on the level of dysfunction. Primary hypothyroidism results from intrinsic thyroid gland dysfunction, causing reduced hormone production despite normal or increased stimulation. Secondary hypothyroidism arises from inadequate thyroid-stimulating hormone (TSH) secretion by the pituitary. Tertiary...