Diet-Dependent Effects of Intracerebroventricular Maresin-1 on Hypothalamus of Rats

Obesity is associated with hypothalamic dysfunction, including altered arcuate nucleus (ARC) signaling-related impairment of energy homeostasis. However, the central metabolic effects of the specialized pro-resolving mediator Maresin-1 (Mar1) remain unclear. This study investigated whether central Mar1 administration alters ARC agouti-related peptide (AgRP), proopiomelanocortin (POMC), and metabolic hormone profiles in rats under standard diet (STD) and high-fat diet (HFD) conditions. Male Wistar albino rats were fed either an STD or an HFD for 12 weeks and assigned to untreated control, vehicle, 50 ng/kg/day Mar1, or 100 ng/kg/day Mar1 groups within each diet condition. Mar1 was administered by continuous intracerebroventricular infusion for 7 days. Body weight, food intake, serum insulin, leptin, ghrelin levels, and ARC AgRP and POMC expressions were evaluated. Central Mar1 infusion did not alter body weight or food intake. In STD-fed rats, 100 ng Mar1 significantly increased serum insulin compared to control (p = 0.025), both Mar1 doses significantly increased leptin versus control (p = 0.0003 and p = 0.0091, respectively), and 50 ng Mar1 significantly increased ghrelin compared with control and vehicle groups (p = 0.0016 and p = 0.0055, respectively). In HFD-fed rats, Mar1 did not significantly change serum hormone levels, and the difference in ghrelin between the 50 ng Mar1 and vehicle groups did not reach statistical significance (p = 0.051). Mar1 did not alter AgRP expression in the ARC under either diet condition. However, under HFD, 100 ng Mar1 increased POMC expression relative to control, vehicle, and 50 ng Mar1 groups (p = 0.0076, p = 0.0078 and p = 0.0204, respectively). Central Mar1 infusion therefore altered circulating metabolic hormones with no significant diet x treatment interaction, and increased ARC POMC expression under HFD, an effect supported by a significant diet x treatment interaction (p = 0.0091), without changing energy intake or body weight over the 7-day infusion. These findings indicate a diet-dependent modulation of hypothalamic melanocortin tone rather than a significant effect on energy balance.