Thyromimetics as emerging therapeutic agents for nonalcoholic steatohepatitis: rationale for the development of resmetirom (MGL-3196).

Hypothyroidism has been linked to certain elements of the metabolic syndrome such as obesity and dyslipidemia which may explain its association with NAFLD. The pathogenesis of NAFLD might be partly attributed to a state of relative intra-hepatic hypothyroidism, a condition of decreased liver thyroid hormone levels. Although...
PUBLISHED IN: Expert Opin Investig Drugs. 2020

Commentary

Hypothyroidism has been linked to certain elements of the metabolic syndrome such as obesity and dyslipidemia which may explain its association with NAFLD. The pathogenesis of NAFLD might be partly attributed to a state of relative intra-hepatic hypothyroidism, a condition of decreased liver thyroid hormone levels. Although the systemic levels of thyroid hormones may stay within the normal range, the intracellular signaling machinery consisting of transporters, deiodinases and receptors are affected in patients with NAFLD.

Therefore, selectivity for a thyromimetic at the predominant liver thyroid hormone receptor, has the potential of providing the metabolic benefits of thyroid hormone and at the same time avoiding unwanted systemic actions. Other pharmacologic strategies to target the thyroid-liver axis include the use of less iodinated versions of the thyroid hormone which has profound effects on lipid metabolism and insulin sensitivity in hepatocytes, and the modulation of deiodinases that can inactivate thyroid hormones.

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Dr. D. Beard

DR. D. BEARD is specialist of Nash Pathology

Articles: 191

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