Abstract
Depression and obesity are common chronic diseases in modern society. Meta-analyses consistently reveal a bidirectional relationship: individuals with depression have a higher risk of obesity, while obese individuals are more prone to depression. High-fat diet (HFD) consumption is a risk factor of obesity. However, the impact of depression on obesity and the underlying mechanisms remains unclear. We aim to assess the impact of a long-term depressive state throughout adulthood on body weight changes induced by HFD, and whether HFD affects depressive state in mice. We established a depression mouse model using a Chronic Unpredictable Mild Stress (CUMS) paradigm. Following the stress period, male mice were fed with a normal diet or a HFD for seven weeks prior to behavioral tests and body weight measurements. Our results suggest that exposure to CUMS initially accelerated weight gain in mice; however, it did not significantly affect final body weight or white adipose tissue weight. Additionally, while HFD did not significantly impact measures of depression-like behavior in CUMS mice but tended to induce depression-like behavior in control mice. Overall, contrary to clinical observations, our findings revealed that a depressive state did not significantly affect the development of obesity in mice, nor did HFD significantly exacerbate depressive-like behaviors in mice.