A unique inflammation-related mechanism by which high-fat diets induce depression-like behaviors in mice

Background: High-fat diet (HFD) consumption is an important reason for promoting depression, but the mechanism is unclear. The present study aims to explore the relationship between metabolic disturbance and HFDinduced depression-like behaviors.Methods: Depression models were established by HFD consumption and chronic unpredictable mild stress (CUMS) in mice. Enzyme-linked immunosorbent assay, western blotting, real-time polymerase chain reaction, gas chromatography and metabolomic analysis were undertaken to investigate the 5-hydroxytryptamine (5-HT) system, neuroinflammation and to identify altered lipid metabolic pathways.Results: Depression-like behaviors, impaired 5-HT neurotransmission and disordered lipid metabolism were observed upon HFD consumption. Despite a similar reduction of high-density lipoprotein cholesterol in CUMS and HFD group, high levels of body low-density lipoprotein cholesterol in the HFD group could help distinguish HFD from CUMS. Levels of interleukin (IL)-1 & beta;, IL-6, tumor necrosis factor (TNF)-& alpha; and inflammation-related metabolites were increased in HFD mice, so a link between depression and inflammation was postulated. Different metabolites were enriched in the two groups. The linoleic acid (LA) metabolic pathway and expression of fatty acid desaturase (FADS)1 and FADS2 (key enzymes in LA metabolic pathway) were enhanced significantly in HFD mice compared with the control group. Limitations: Causality analyses for HFD and inflammation-related features were not undertaken. Conclusions: HFD-induced depression-like behaviors was characterized by more severely disordered metabolism of lipids (especially in the LA metabolic pathway) and increased levels of inflammatory mediators, which might be the reasons for the disturbance of serotonergic system in hippocampus.

Automated summary

This study found that high-fat diet is associated with depression and metabolic disturbance. Through experiments on mice, it was found that high-fat diet leads to depression-like behaviors, impaired serotonergic system, and disordered lipid metabolism. In addition, levels of inflammatory mediators were increased, suggesting a possible link between depression and inflammation. High-fat diet also enhances the linoleic acid metabolic pathway, further exacerbating lipid metabolism disorders. These findings contribute to the understanding of the relationship between depression and metabolic disturbance.