Enhanced metabolic benefits of dietary methionine restriction in cold resistant hybrid UCP1-deficient mice

Document Type

Article

Publication Date

2-3-2026

Institution/Department

Center for Molecular Medicine

Journal Title

The Journal of nutritional biochemistry

Abstract

Dietary methionine restriction (MR) improves metabolic health in various animals. Beneficial effects on mice include reduced obesity and improved metabolism associated with the appearance of multilocular uncoupling protein 1 (UCP1) positive adipocytes in white fat. This suggests that MR-induced UCP1 thermogenesis contributes significantly to metabolic health. To test this, we evaluated MR effects using unique UCP1-deficient mice on a hybrid (F1) background that is resistant to developing hypothermia upon acute cold exposure. F1.Ucp1 and F1.Ucp1 mice were fed high fat control diet (HF-CD) and then switched to a high fat MR diet (HF-MRD). Indirect calorimetry was used to monitor energy metabolism; and, serum hormones, metabolites, tissue gene expression, and histology were evaluated. While both genotypes showed improved metabolic parameters when fed HF-MRD, F1.Ucp1 mice exhibited further changes in iWAT morphology and more pronounced metabolic improvements in glucose tolerance, serum metabolic biomarker profiles and hepatic steatosis compared to F1.Ucp1. Strikingly, F1.Ucp1 mice showed elevated fatty acid oxidation compared with F1.Ucp1 when fed high fat control diet (HF-CD) that was sustained after the switch to HF-MRD. We posit that F1.Ucp1 mice employ fatty acid oxidation for body temperature maintenance as at least a part of a mechanism that protects them from acute exposure to cold temperatures in addition to development of diet-induced obesity. Furthermore, our studies suggest that many of the metabolic benefits of MR in mice do not require functional UCP1 thermogenesis.

First Page

110299

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