Aims
The present study was designed to compare the effects of a low-fat diet (LF), calorie restriction (CR), quercetin (Que) and exercise (Ex) on hepatic steatosis in a high-fat (HF) diet-induced obesity prone (OP) model in the perspective of microRNA (miR)-dependent thyroid hormone (TH) synthesis and action. Main
Methods
Male C57BL/6J mice were administered a HF diet for 10 weeks to induce OP phenotype and then divided into 5 groups, HF diet (OP-HF), LF diet (OP-LF), 70% CR (OP-CR), 0.05% Que (OP-Que) and a treadmill exercise regimen (OP-Ex); one additional group fed LF diet served as control (LF). 7 weeks later, serum indexes, metabolic alterations, redox status and histological appearance in the thyroid and liver, and TH related miRs with their targets expressions were determined. Key findings: No significance on T3 levels was observed among the six groups. LF, CR, Que and Ex significantly ameliorated HF-induced hepatic steatosis to varying degrees, inhibited T4 production via differentially elevating miR-339, miR-383 and miR-146b to decrease NIS expression and regulating miR-200a/Nrf2 to maintain redox status in the thyroid. Furthermore, these four interventions differentially and significantly decreased miR-383 and miR-146b to elevate TRb and DIO1 expression, and subsequent TH responsive lipid metabolism genes regulation. Among them, the effects of CR on hepatic steatosis were the most prominent. Significance: Our data indicated that amelioration of hepatic steatosis by LF, CR, Que and Ex resulted in many shared, but also many differential changes in the miR-dependent TH production and action.
Significance
Our data indicated that amelioration of hepatic steatosis by LF, CR, Que and Ex resulted in many shared, but also many differential changes in the miR-dependent TH production and action.