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Purpose: Obesity is associated with neuroendocrine and metabolic dysregulation, yet the underlying mechanisms remain incompletely understood. This study aimed to investigate how pituitary hormonal axes and peripheral hormones respond to a cafeteria diet or a calorie-restricted diet in rats.

Methods: Ten-week-old male Wistar rats (n = 36) were randomized (1:1:1) to one of three diets for 12 weeks: an ad libitum standard rat chow diet (control group); an ad libitum cafeteria diet, containing cheese doodles, chocolate balls and salted peanuts, in addition to standard chow (diet-induced obesity group, DIO); or calorie-restriction (aiming at 85% body weight of controls; restricted group). We assessed endocrine gland weights, plasma levels of pituitary hormones and related peripheral signals, and explored their associations with metabolic and behavioral outcomes.

Results: While the DIO group exhibited increased body weight, insulin resistance, and altered metabolic markers, only modest changes in pituitary hormones were observed, with a reduction in luteinizing hormone (p < 0.05). Correlation analysis showed that when combining the control and DIO groups, prolactin inversely correlated with exploratory-activity (rho =-0.458, p < 0.05) from the behavioral test. In contrast, the restricted group showed more pronounced hormonal changes, including reduced levels of adrenocorticotropic hormone (p < 0.01), prolactin, and thyroid-stimulating hormone (both p < 0.05) as well as insulin-like growth factor-1 (p < 0.01). Multivariate data analysis showed a clear separation of the DIO group from the other groups, mainly driven by metabolic variables.

Conclusion: Despite notable metabolic perturbations in the DIO group, the absence of endocrine changes suggests a partly different phenotype than what is typically observed in humans with obesity.