The Role of Ghrelin, Neuropeptide Y and Leptin Peptides in Weight Gain after Deep Brain Stimulation for Parkinson’s Disease

Abstract

Background: The exact mechanism of weight gain (WG) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with idiopathic Parkinson’s disease remains unknown. Objectives: To investigate a possible involvement of ghrelin, neuropeptide Y (NPY) and leptin in WG after DBS. Methods: Twenty-three Parkinson patients were submitted for body composition measurements and blood sampling 3 days before, and 3 and 6 months after STN DBS. Peripheral concentrations of ghrelin, NPY, and leptin were determined, as well as the L-dopa equivalent daily dose. Patients were clinically evaluated using the Unified Parkinson’s Disease Rating Scale. Results: Three months after surgery, a significant WG was observed (3.09 ± 5.00 kg; p = 0.007) with no further increase at 6 months. Three months postoperatively, NPY circulating levels increased significantly (p = 0.05), while the increase of ghrelin levels reached statistical significance at 6 months (p = 0.001). WG was significantly associated with changes of ghrelin and leptin levels at 3 and 6 months, respectively. Conclusions: STN DBS seems to temporarily dysregulate the hypothalamic secretion of NPY and ghrelin. The variation of weight may be attributed to an increased production of ghrelin and leptin. A possible neuroprotective role of DBS, exerted through the increase of ghrelin levels, should be further studied.

Decrease in Blood Cortisol Corresponds to Weight Gain following Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson’s Disease

“…The WG following STN DBS might thus mean a compensation of previous loss, rather than an excessive anabolic reaction. Accordingly, we suspect that the observation of a more sustained WG in our group may correspond to a lower initial body mass index than that reported by Markaki et al (25.8 vs. 28.7), leading to a continued increase in weight in our patients, even if initial values were well above undernutrition in both groups [4,5]. …”

“…However, the mechanisms underlying this weight gain (WG) remain unclear. We, therefore, read with great interest the recently published article ‘The role of ghrelin, neuropeptide Y and leptin peptides in weight gain after deep brain stimulation for Parkinson’s disease’ by Markaki et al [4]. The authors performed body composition measurements and blood sampling before, and 3 and 6 months after STN DBS in 23 PD patients, looking for relations between WG and changes in blood levels of the metabolic hormones ghrelin, neuropeptide Y (NPY) and leptin.…”

“…Curiously enough, Markaki et al [4] do not pay much attention to their own finding of markedly decreased cortisol levels following STN DBS. Nevertheless, this result is in surprisingly precise agreement with our observation, probably shedding more light on the mechanisms of WG in PD following STN DBS (table 1).…”

“…Nevertheless, this result is in surprisingly precise agreement with our observation, probably shedding more light on the mechanisms of WG in PD following STN DBS (table 1). At 3 months after STN DBS, Markaki et al [4] noticed a significant decrease in blood cortisol (–23.8%, p = 0.027). In our study, cortisol levels decreased at 2 months, (–23.9%, p < 0.002), still remaining significantly reduced compared to baseline at 12 months after DBS implantation (–22.9%, p = 0.008) [5].…”

Deep-Brain Stimulation for Parkinson's Disease

“…Furthermore, many reports suggested the possibility of significant weight increase after DBS in advanced PD, creating some concern among patients, especially in cases of obesity, diabetes, and other metabolic disorders [9]. It is thought to be secondary to reduction in the metabolic rate after resolution of tremor and/or dyskinesia and/or a direct stimulation effect on appetite centers [10][11][12]. In an original article, S. H. Millan et al report different findings in early PD and offer insightful explanation to the difference.…”