New Insights into Regulation of Lipid Metabolism by Thyroid Hormone

Overview

Journal Curr Opin Endocrinol Diabetes Obes

Specialty Endocrinology

Date 2010 Jul 21

PMID 20644471

Citations 33

Authors

Xuguang Zhu

Sheue-Yann Cheng

Affiliations

Soon will be listed here.

Abstract

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(PV) mouse) or the Thrb gene (Thrb(PV) 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(PV) mice, but not in Thrb(PV) 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(PV) mice. In contrast, reduced expression of genes critical for lipogenesis mediates decreased liver mass with lipid scarcity in Thra1(PV) mice.

Summary: Studies using Thra1(PV) and Thrb(PV) 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.

Citing Articles

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The Prevalence of Metabolic Syndrome among Adult Filipinos with Hypothyroidism: A Retrospective Cohort Study.

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Characteristics and Prevalence of Metabolic Syndrome Among Adult Filipinos with Hypothyroidism: A Cross-sectional Study.

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Thyroid Hormone and Mitochondrial Dysfunction: Therapeutic Implications for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

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Association between thyroid function and diabetes peripheral neuropathy in euthyroid type 2 diabetes mellitus patients.

He Q, Zeng Z, Zhao M, Ruan B, Chen P Sci Rep. 2023; 13(1):13499.

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