Dietary Methionine Restriction Promotes Fat Browning and Attenuates Hepatic Lipid Accumulation in High-Choline-Fed Mice Associated with the Improvement of Thyroid Function

This study aims to explore the influences of a methionine-restricted diet (MRD) on fat browning and hepatic lipid accumulation in mice fed with a high-choline diet (HCD) and their possible mechanisms. ICR mice were randomly divided into three groups and fed with a normal diet (0.86% methionine + 0.20% choline, ND), HCD (0.86% methionine + 1.20% choline), or MRD (0.17% methionine + 1.20% choline) for 90 consecutive days. We found that MRD reduced body weight and fat mass; increased heat production and ambulatory locomotor activity; reduced hepatic and plasma lipid levels, hepatic fatty infiltration area, and adipocyte volume in white and brown adipose tissue; promoted fat browning, especially upregulated gene and protein expression levels of uncoupling protein 1 (UCP1); and promoted fat catabolism and inhibited fat anabolism in the liver and adipose tissue. Moreover, MRD increased antioxidant defenses and reduced inflammatory cytokine levels in the thyroid, blood, and liver. Furthermore, MRD improved thyroid morphological structure, promoted the synthesis and secretion of thyroid hormones, and enhanced the actions of thyroid hormones on its receptor organs (liver and adipose tissue). These findings suggested that MRD promoted fat browning and attenuated hepatic lipid accumulation in HCD mice associated with the improvement of thyroid function.