Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD

Abstract

Thyroid hormones control lipid metabolism by exhibiting specific effects on the liver and adipose tissue in a coordinated manner. Different diseases of the thyroid gland can result in hypothyroidism. Hypothyroidism is frequently associated with dyslipidemia. Hypothyroidism-associated dyslipidemia subsequently results in intrahepatic accumulation of fat, leading to nonalcoholic fatty liver disease (NAFLD), which leads to the development of hepatic insulin resistance. The prevalence of NAFLD in the western world is increasing, and evidence of its association with hypothyroidism is accumulating. Since hypothyroidism has been identified as a modifiable risk factor of NAFLD and recent data provides evidence that selective thyroid hormone receptor β (THR-β) agonists are effective in the treatment of dyslipidemia and NAFLD, interest in potential therapeutic options for NAFLD targeting these receptors is growing. In this review, we summarize current knowledge regarding clinical and molecular data exploring the association of hypothyroidism, dyslipidemia and NAFLD.

Associations of phthalates with NAFLD and liver fibrosis: A nationally representative cross-sectional study from NHANES 2017 to 2018

“…A recent study demonstrated that positive association between the urine levels of phthalate metabolites and NAFLD was observed in adults with subclinical hypothyroidism, but not in those with euthyroidism ( 30 ). In fact, evidence of a higher prevalence of NAFLD in patients with hypothyroidism has been detailed recorded in previous literature ( 23 , 31 ). Thyroid hormones mainly activate TH-Receptor β, a potential target in NAFLD therapy, and thus may improve liver steatosis ( 32 , 33 ).…”

Diagnostic Features and Selection of Hypolipidemic Therapy in Patients with Coronary Artery Disease with “Possible” Familial Hypercholesterolemia

“…Трийодтиронін зумовлює посилення регуляції рецепторів ЛПНЩ, контролює стерол-регуляторний білокзв'язуючий елемент-2 (SREBP-2), який, у свою чергу, модулює експресію гена рецептора ЛПНЩ і захищає ЛПНЩ від окиснення. Гормони щитоподібної залози впливають на метаболізм ЛПВЩ, підвищуючи активність білка, що переносить складні ефіри холестерину (cholesterol ester transfer protein, СЕТР) та стимулює ліпопротеїнліпазу, яка катаболізує ліпопротеїни, багаті на ТГ, печінкову ліпазу і сприяє перетворенню ліпопротеїнів проміжної щільності в ХС ЛПНЩ [11].…”

Sensitivity to thyroid hormones is associated with advanced fibrosis in euthyroid patients with non-alcoholic fatty liver disease: A cross-sectional study

“…Researchers also found that higher serum TSH and lower FT4 concentrations were significantly associated with steatosis and fibrosis in NAFLD [11 , 12] . Hypothyroidism-induced NAFLD has been attributed to decreased lipid utilization, including reduced β-oxidation of free fatty acids (FFAs) and the clearance of TGs, with a consequent increase in the accumulation of TGs and low-density lipoprotein within hepatocytes [13] . Moreover, hypothyroidism is correlated with hepatic insulin resistance, which fails to suppress the production of endogenous glucose and stimulates DNL [14] .…”