Reduced serum adiponectin and exercise predict depression in chronic heart failure patients and affect depressive-like behaviors in a mouse model.

Background: Chronic heart failure (CHF) is frequently comorbid with depression and anxiety. Currently, we aim to investigate the association between serum adiponectin levels and depression among patients with CHF. Methods: A total of 119 patients with HF in a tertiary hospital in southern China were enrolled. All patients completed the Patient Health Questionnaire-9 (PHQ-9) upon discharge. Serum levels of adiponectin, ghrelin, leptin A, and BDNF were measured. On the basis of PHQ-9 scores, HF patients were divided into non-Dep, mild-Dep, moderate-Dep, and severe-Dep groups. Differences in the levels of cardiac markers and serum mediators between the non/mild-Dep group and the moderate/severe-Dep group were analyzed using weighted univariate and multivariate logistic regression models. An HF C57BL/6 mouse model of depression was established. AdipoRon, an orally active adiponectin receptor agonist, was administered to the mouse model. Results: A total of 119 patients with CHF were categorized into non-Dep (n=35), mild-Dep (n=46), moderate-Dep (n=20), and severe-Dep groups (n=18). Compared with those in the non-Dep group, adiponectin levels in the Dep group were significantly lower and correlated with increased depression severity in HF patients. Weighted univariate and multivariate regression analyses indicated that adiponectin (OR = 0.719; 95% CI: 0.531-0.975) and exercise duration (OR = 0.655; 95% CI: 0.489-0.877) were potential predictors of CHF comorbid with depression. Spearman correlation analysis revealed a positive correlation between adiponectin levels and exercise frequency/duration, whereas negative correlations were found between depression scores and exercise frequency/duration. Sensitivity analyses with stepwise exclusion of high-risk subgroups (diabetes, systemic inflammation, and severe HF) revealed a significant association between exercise duration and depression. In a depression model in MI mice, serum adiponectin levels were decreased. Compared with single-treatment approaches, the combination of adiponectin receptor agonists and exercise intervention effectively improved depressive-like behaviors in mice and regulated related biomarker levels, with superior effects. Conclusion: Reduced serum adiponectin levels and exercise activity were associated with increased odds of having CHF comorbid with depression. Activation of the adiponectin/AdipoR1 pathway combined with exercise intervention has potential benefits for the prevention of depression in patients with HF.