MicroRNA-124–3p regulates NPY to affect appetite in individuals with depressive disorder

While the pathogenesis of depression has been extensively studied, the mechanisms underlying appetite suppression in depression remain poorly understood. This study aimed to elucidate the role of the microRNA-124-3p (miR-124-3p)/neuropeptide Y (NPY) axis in regulating appetite during depression. We examined the relationship between body weight fluctuations and serum miR-124-3p/NPY levels in major depressive disorder (MDD) patients and assessed correlations between NPY levels and appetite scores. Chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS)-induced depression mouse models were established to monitor food intake and body weight fluctuations. Hippocampal and cortical tissues were collected to measure miR-124-3p and NPY expression. The miR-124-3p antagomir (inhibitor) and agomir (activator) were subsequently administered to LPS-induced mice to evaluate changes in NPY expression. Clinical studies have confirmed the interactions among miR-124-3p, NPY, and appetite regulation. MDD patients presented elevated serum levels of miR-124-3p, reduced NPY content, and a positive correlation between NPY levels and both appetite scores and body weight. In depression model mice, miR-124-3p expression was increased in the hippocampus and cortex, whereas NPY expression was decreased. Inhibition of miR-124-3p activity enhanced NPY expression, leading to weight gain. Conversely, the activation of miR-124-3p reduces NPY expression, resulting in weight loss. Our study demonstrated that miR-124-3p negatively regulates NPY to mediate appetite suppression in depression. Targeting this axis could provide novel therapeutic strategies for managing weight loss and appetite dysfunction in MDD patients.