The obesity-depression connection: experimental evidence with translational potential for clinical practice

Abstract

Introduction: Obesity, in addition to its metabolic repercussions, has been associated with an increased risk of depression. Investigating this relationship in experimental models is essential to elucidate the underlying mechanisms and to inform preventive and therapeutic strategies. Objective: To investigate obesity as a risk factor for the development of behavioral changes associated with depression through behavioral assessment and hormonal analysis in an experimental rat model. Method: Immediately after birth, litters were randomly organized and standardized to 10 pups per dam, prioritizing males. During this period, maternal separation protocols were applied to induce depressive-like states, while litter size reduction was employed to induce obesity. At 220 days of age, animals underwent the Modified Forced Swim test and the Sucrose Preference test. At the end of the experiment euthanasia was performed and blood samples were collected for plasma corticosterone analysis. Result: Animals in the depressive group exhibited significantly longer immobility times in the Modified Forced Swim test (p≤0.05), indicating a depressive-like behavioral phenotype, whereas the obese group did not differ from the control group. No statistically significant differences among groups were observed in the Sucrose Preference test or in water and sucrose intake. Hormonal analysis revealed significantly elevated plasma corticosterone levels in the depressive group compared with the control and obese groups, which did not differ from each other. Conclusion: In the experimental model used, obesity was not characterized as a risk factor for depression, since corticosterone levels and performance on behavioral tests remained similar to those observed in the control group. In contrast, early stress induced by maternal separation produced significant behavioral and hormonal changes, highlighting its important role in inducing the depressive phenotype. These findings reinforce the complexity of the interaction between obesity and depression and suggest that other modulating factors may influence this relationship.