Drug Discov Today. 2025 Oct 24:104509. doi: 10.1016/j.drudis.2025.104509. Online ahead of print.
ABSTRACT
The pathophysiology of obesity and depression, frequent comorbidities of our modern society, involves a predominant role of adipocytokines. Dysregulated adipocytokines, including leptin, adiponectin, and resistin, promote chronic low-grade inflammation, neuroendocrine imbalances, and a neuroplasticity deficit. These adipocytokines trigger the hypothalamic-pituitary-adrenal (HPA) axis, increasing cortisol levels and ultimately inducing hyperphagia and affective symptoms. Adipocytokines also modulate the neurotransmitter systems essential for mood regulation and cognitive functions. In this review, we explore the role of adipocytokines as bidirectional links between obesity and depression, highlighting them as novel druggable targets for treating comorbid obesity and depression.
PMID:41201620 | DOI:10.1016/j.drudis.2025.104509
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