Chronic psychosocial defeat differently affects lipid metabolism in liver and white adipose tissue and induces hepatic oxidative stress in mice fed a high-fat diet.

It is widely accepted that chronic stress may alter the homeostatic mechanisms of body weight control. In this study, we followed the metabolic changes occurring in mice when chronic stress caused by psychosocial defeat (CPD) is associated with ad libitum exposure to a palatable high-fat diet (HFD). In this model, CPD mice consumed more HFD than unstressed (Un) mice without gaining body weight. We focused on metabolic processes involved in weight control, such as de novo lipogenesis (DNL), fatty acid β-oxidation (FAO), and thermogenesis. The activity and expression of DNL enzymes were reduced in the liver and white adipose tissue of mice consuming the HFD. Such effects were particularly evident in stressed mice. In both CPD and Un mice, HFD consumption increased the hepatic expression of the mitochondrial FAO enzyme carnitine palmitoyltransferase-1. In the liver of mice consuming the HFD, stress exposure prevented accumulation of triacylglycerols; however, accumulation of triacylglycerols was observed in Un mice under the same dietary regimen. In brown adipose tissue, stress increased the expression of uncoupling protein-1, which is involved in energy dissipation, both in HFD and control diet-fed mice. We consider increased FAO and energy dissipation responsible for the antiobesity effect seen in CPD/HFD mice. However, CPD associated with HFD induced hepatic oxidative stress