Sleeve gastrectomy alleviates anxiety-like behaviors in mice with high-fat diet induced obesity

Abstract

The efficacy of bariatric surgery (BS) in alleviating obesity-associated anxiety symptoms remains unclear. This study aimed to investigate the impact of BS on anxiety using an obese mouse model, elucidating the complex interplay between obesity, anxiety, and related biological factors. Sleeve gastrectomy (SG) was performed on mice rendered obese via a high-fat diet to establish a BS model. The influence of SG on anxiety-like behaviors, amygdala gene expression, serum metabolite profiles, and gut microbiota composition was systematically evaluated. Behavioral analyses demonstrated that obesity intensified anxiety-like behaviors, whereas SG markedly mitigated these symptoms. Transcriptomic analysis revealed that SG altered gene transcription patterns in the amygdala, particularly affecting neurotransmitter and receptor genes. Serum metabolomics further validated these findings, indicating significant changes in neurotransmitter metabolite levels. Additionally, surgically treated mice exhibited elevated serum inosine concentrations, a microbial-derived metabolite, aligning with increased abundance of the inosine-producing bacterium Akkermansia muciniphila post-surgery. Given the rising global prevalence of obesity and associated mental health complications, understanding the potential mental health benefits of BS is critical. This study provides preclinical evidence supporting the anxiolytic effects of BS and underscores the need for further research to clarify its implications for human mental health.