Effect of the hypothalamic serotonin on body weight change in the context of brain insulin resistance in Alzheimer’s disease

Aims: The present work was designed to evaluate how alterations in serotonin (5-hydroxytryptamine, 5-HT), 5-HT receptor subtype 2B (5-HT2BR), and neuropeptide Y (NPY) are associated with body weight regulation in a rat model of brain insulin resistance (B-IR) that mimics the early pathological features of Alzheimer’s disease (AD). Methods: B-IR was induced in rats through intracerebroventricular (i.c.v.) administration of amyloid-β₁–₄₂ oligomers at a dose of 2.5 nmol in a total volume of 10 μL. 5-HT concentrations were quantified in brainstem and hypothalamic samples, while hypothalamic levels of 5-HT2BR and NPY were determined using enzyme-linked immunosorbent assay (ELISA) methods. Body weight variation for each animal was defined as the difference between post-experimental and initial measurements. Group comparisons were conducted using the Mann–Whitney U test, and statistical significance was accepted at p < 0.05. Results: Rats in the B-IR group showed a tendency toward increased 5-HT levels in brainstem tissue compared to the control group (p > 0.05), whereas hypothalamic 5-HT levels were significantly decreased in the B-IR group compared to controls (p < 0.01); body weight was significantly reduced in the B-IR group compared to the control group (p<0.01). In addition, rats in the B-IR group showed a downward trend in hypothalamic 5-HT2BR and NPY levels compared with the control group (p > 0.05 for both). Conclusion: These findings suggest that decreased hypothalamic 5-HT levels in the B-IR group may be associated with the observed reduction in body weight. Additionally, the downward trends observed in 5-HT2BR and NPY levels may also be related to this change.