New insights into regulation of lipid metabolism by thyroid hormone.
Summary of "New insights into regulation of lipid metabolism by thyroid hormone."
PURPOSE OF
REVIEW:
Thyroid hormone (3,3',5-triiodo-L-thyronine) plays an important role in thermogenesis and maintenance of lipid homeostasis. The present article reviews the evidence that 3,3',5-triiodo-L-thyronine regulates lipid metabolism via thyroid hormone receptors, focusing particularly on in-vivo findings using genetically engineered mice. RECENT
FINDINGS:
That lipid metabolism is regulated via thyroid hormone receptor isoforms in a tissue-dependent manner was recently uncovered by using knockin mutant mice harboring an identical mutation in the Thra gene (Thra1 mouse) or the Thrb gene (Thrb mouse). The mutation in the Thra gene dramatically decreases the mass of both white adipose tissue and liver. In contrast, the mutation in the Thrb gene markedly increases the mass of liver with an excess depot of lipids, but no significant abnormality is observed in white adipose tissue. Molecular studies show that the expression of lipogenic genes is decreased in white adipose tissue of Thra1 mice, but not in Thrb mice. Markedly increased lipogenic enzyme expression, and decreased fatty acid beta-oxidation activity contribute to the adipogenic steatosis and lipid accumulation in the liver of Thrb mice. In contrast, reduced expression of genes critical for lipogenesis mediates decreased liver mass with lipid scarcity in Thra1 mice.
SUMMARY:
Studies using Thra1 and Thrb mice indicate that apo-thyroid hormone receptor-beta and apo-thyroid hormone receptor-alpha-1 mediate distinct deleterious effects on lipid metabolism. Thus, both thyroid hormone receptor isoforms contribute to the pathogenesis of lipid abnormalities in hypothyroidism, but in a target tissue-dependent manner. These studies suggest that thyroid hormone receptor isoform-specific ligands could be designed as therapeutic targets for lipid abnormalities.
Affiliation
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Journal Details
This article was published in the following journal.
Name: Current opinion in endocrinology, diabetes, and obesity
ISSN: 1752-2978
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20644471
- DOI: http://dx.doi.org/10.1097/MED.0b013e32833d6d46
Medical and Biotech [MESH] Definitions
Thyroid Hormone Resistance Syndrome
An inherited autosomal recessive trait, characterized by peripheral resistance to THYROID HORMONES and the resulting elevation in serum levels of THYROXINE and TRIIODOTHYRONINE. This syndrome is caused by mutations of gene THRB encoding the THYROID HORMONE RECEPTORS BETA in target cells. HYPOTHYROIDISM in these patients is partly overcome by the increased thyroid hormone levels.
Receptors, Thyroid Hormone
Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.
Lipidoses
Conditions characterized by abnormal lipid deposition due to disturbance in lipid metabolism, such as hereditary diseases involving lysosomal enzymes required for lipid breakdown. They are classified either by the enzyme defect or by the type of lipid involved.
Thyrotoxicosis
A hypermetabolic syndrome caused by excess THYROID HORMONES which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid HYPERPLASIA; THYROID NEOPLASMS; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by NERVOUSNESS; TACHYCARDIA; FATIGUE; WEIGHT LOSS; heat intolerance; and excessive SWEATING.
Triiodothyronine
A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.
PubMed Articles
Thyroid hormone action in metabolic regulation.
Thyroid hormone plays pivotal roles in growth, differentiation, development and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. The transcri...
New insights into thyroid hormone actions and lipid metabolism.
A case of resistance to thyroid hormone with thyroid cancer.
Resistance to thyroid hormone (RTH) is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features. The magnitude of RTH is caused by m...
Mechanisms of thyroid hormone action.
Our understanding of thyroid hormone action has been substantially altered by recent clinical observations of thyroid signaling defects in syndromes of hormone resistance and in a broad range of condi...
Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affec...
Clinical Trials
LDL-Cholesterol Lowering Effect of KB2115 as Add on to Statin
Thyroid hormones are known to reduce cholesterol levels through regulation of a number of key enzymes involved in synthesis, degradation, and lipid transport. However, the currently marke...
Effects of Chronic Insomnia on the Neuroendocrine Regulation of Glucose and Lipid Metabolism
We aim to assess the influence of chronic insomnia on the neuroendocrine regulation of the glucose and lipid metabolism to more clearly define the metabolic derangements associated with ch...
Human thyroglobulin (Tg) is the most sensitive biochemical marker for recurrence of differentiated cancer (DTC), especially after the complete removal of thyroid tissue through surgery and...
RATIONALE: Radioactive iodine uses radiation to kill tumor cells. Giving iodine I 131 with or without thyroid-stimulating hormone after surgery may kill any tumor cells that remain after s...
This study intends to examine how a common genetic pattern affects thyroid function. Recent studies have demonstrated that a substance (enzyme) produced by a gene has an important role in...
