Melanotan II, mirroring time-restricted feeding, lowers blood pressure without weight loss in rats on a high-fat diet

Managing obesity-related hypertension is a significant clinical challenge. While weight loss through lifestyle changes can lower blood pressure, long-term adherence to such interventions is notoriously poor, limiting their effectiveness. This has spurred research into alternative or complementary strategies. Emerging evidence suggests that the timing of food intake, independent of total calories, plays a crucial role in regulating metabolic health and blood pressure. This paper investigates whether confining feeding to the body's natural active phase can be a viable method to control blood pressure, even without the often-difficult goals of caloric restriction and weight reduction. The study uses a pharmacological approach with an α-MSH analog, Melanotan II, to mimic this feeding pattern and test its cardiovascular effects.

The research involved two parallel studies using rats fed a high-fat diet (HFD). In study 1, one group of rats had 24-hour ad libitum access to food (Control), while the other was subjected to time-restricted feeding (TRF), with food available only for 12 hours during their active dark phase. In study 2, HFD-fed rats were administered either saline (Control) or a long-acting α-MSH analog, Melanotan II (MTII). One MTII group received the injection at light onset (MTII light) to shift feeding to the active phase, while the other received it at dark onset (MTII dark). The primary endpoints measured were food intake, body weight, fat mass, and blood pressure (systolic and mean arterial pressure).

In Study 1, both the Control and TRF groups consumed the same amount of food and had no significant differences in body weight gain or fat mass accumulation. Despite this, the TRF group, which ate only during their active phase, exhibited lower systolic and mean arterial pressure (MAP). In Study 2, both MTII groups (light and dark onset) showed significantly reduced food intake compared to the saline Control group. However, there was no difference in final body weight or fat mass between the two MTII groups. Critically, the MTII light group, which consumed most of its calories during the active dark phase (similar to the TRF rats), also displayed lower MAP.

The consistent finding across both pharmacological and behavioral interventions was that rats consuming their calories predominantly during the active phase displayed lower mean arterial pressure. This effect was observed even when caloric intake and body fat were identical to control groups (TRF vs. Control) or when body fat was similar between intervention groups (MTII light vs. MTII dark), isolating feeding time as the key variable.