Evaluation of the hepatic and subcutaneous adipose tissue effects of triiodothyronine treatment in an animal model of metabolic syndrome.

Background and aims: Metabolic dysfunction associated steatotic liver disease (MASLD) is a metabolic liver disease and thyroid hormones (TH) may decrease liver fat and extra-hepatic fat content. We aimed to evaluate the effects of high and low dose triiodothyronine (T3) in liver and subcutaneous adipose tissue (sAT) in an animal model of Metabolic Syndrome (MS).

Methods and results: Four groups were evaluated: 1) ZSF1 Lean (Lean-Ctrl, n = 8); 2) ZSF1 obese (rat model of MS with MASLD, MetS, n = 13); 3) ZSF1 obese supplemented with high-dose of T3 (MetS-hT3, n = 5); and 4) ZSF1 obese supplemented with a low-dose of T3 (MetS-lT3, n = 8). Treatment with both doses of T3 decreased body weight, liver weight and perirenal fat. High-dose T3 treatment normalized the increased expression of COL3A1 in MetS group. Histologically, lipid hepatic burden in treated groups was significantly reduced. Adipocytes and adipocytes' fibrosis areas were significantly reduced by the treatment with T3. MetS-hT3 had an increased risk of arrhythmias and sudden death.

Conclusion: Treatment with T3 improves steatosis and fibrosis at the liver and sAT in animals with MS. High doses of T3 may not be safe due to the risk of cardiac events. Our results support new therapeutic strategies for MASLD focused on the modulation of TH.