The background of previous studies on the anti-obesity mechanism of MAO-B inhibitors and the clinical verification of our study were comprehensively illustrated in a schematic diagram (Fig. 1). In general, we observed a slight but insignificant trend of weight loss by iMAO-Bi among PD patients by multiple verifications. We reported for the first time the anti-obesity effects of iMAO-Bi in both short-term and long-term administrations. According to our small-scale cohort study, iMAO-Bi did not show a significant anti-obesity impact in patients with PD, which was consistent with the results of animal experiments [3]. However, it may be too early to draw a conclusion. Previous studies have reported that selegiline can significantly reduce astrocytic reactivity in the short term in AD model mice by markedly suppressing hypertrophy and astrogliosis in addition to astrocytic GABA, which may also be applied to weight loss mechanisms in humans [6,7,8]. Furthermore, selegiline has protective effects against inflammatory response, oxidative stress, and hepatic lipid metabolism by reducing the expression of proinflammatory cytokines [9]. Our study showed a possible trend of weight loss in a short-term iMAO-Bi treatment compared with the long-term treatment. Moonsun et al. also suggested that selegiline caused a transient reduction in body weight before the turning-on of the GABA-synthesizing enzyme diamine oxidase [3, 4]. Thus, more comprehensive large-scale studies and experiments should be performed to verify the clinical anti-obesity effectiveness of iMAO-Bi, either in a short-term or long-term treatment. On the other hand, rMAO-Bi is becoming a promising alternative anti-obesity drug by reversibly occupying the active site of MAO-B without inducing compensatory mechanisms [3, 4], which should be verified in further study.

This diagram summarizes previous research in the sections “Background” and “Mice model”. Our study, which verifies the potential anti-obesity effects on humans, is presented in the “Clinical verification” section. Key points for future research are highlighted in the lower section.

There are several limitations in our study. One concern about the findings was the limited sample size in our study. We only included patients with multiple admissions, as they had comprehensive clinical evaluations in medical history and laboratory results. Additionally, we only included patients with PD in our study, while patients with other neurological disorders administrated with iMAO-Bi should also be involved. This study may also be limited by potential confounders, which could not be fully corrected in a retrospective study. Despite these, our results shed light on how iMAO-Bi can affect human body weight and pave the way for larger scales of clinical research and the development of anti-obesity drugs.