Abstract
For patients with a craniopharyngioma (CP), treatment of hypothalamic obesity (HO) and hyperphagia following resection and/or radiotherapy is extremely difficult and few reports have been published on potential drug therapies. Psychomotor stimulant methylphenidate (MPH) has been reported to inhibit food intake (FI). In this paper, we report reduction of body mass index (BMI) and appetite in an adolescent CP patient suffering from HO. We then tested the ability of MPH to attenuate the FI and body weight (BW) gain in a rat model consistent with the neuroanatomical and metabolic disturbances commonly observed in obese CP patients. Specifically, we used a novel electrolytically generated combined medial hypothalamic lesion (CMHL) affecting the arcuate nucleus, ventromedial hypothalamic nucleus, and dorsomedial hypothalamic nucleus to induce hyperphagia, rapid weight gain, and adiposity. Both CMHL and control animals (n = 7 per group) were administered either methylphenidate HCl (MPH; 20 mg kg−1 day−1) or saline for 4 days in a crossover design experiment 28 weeks post-surgery. A significant decrease in percent baseline FI (CMHL −23%, p = 0.008; control −20%, p = 0.002) and percent change in BW (CMHL −1.97%/4 days, p = 0.011; control −1.75%/4 days, p = 0.003) was observed during MPH treatment as compared to saline. Conclusion: This study shows MPH treatment of severely obese CMHL rats resulted in significantly reduced FI and BW loss.
Highlights
Severe hypothalamic obesity (HO) and hyperphagia are common sequelae following tumor resection in child and adolescent craniopharyngioma (CP) patients, ranging in rate from 22 to 62% (Brauner et al, 1987; Sorva, 1988; Muller, 2008)
We developed a novel combined medial hypothalamic lesion (CMHL) model that utilizes electrolytic lesions in the arcuate nucleus (ARC), ventromedial hypothalamic nucleus (VMN), and dorsomedial hypothalamic nucleus (DMN) to model the sequelae commonly observed in HO resulting from resection and/or treatment of CP (Roth et al, 2011a)
Pre-surgery body weight (BW), body length (BL), and LI were comparable in lesion and control groups (p = 0.539, p = 0.533, p = 0.122, respectively)
Summary
Severe hypothalamic obesity (HO) and hyperphagia are common sequelae following tumor resection in child and adolescent craniopharyngioma (CP) patients, ranging in rate from 22 to 62% (Brauner et al, 1987; Sorva, 1988; Muller, 2008). Post-resection and/or treatment, a distinct trend in weight gain has been observed in children who developed HO. Pharmacological treatment of HO and hyperphagia has shown success in a few clinical studies and case reports (Mason et al, 2002; Lustig et al, 2003; Danielsson et al, 2007; Hamilton et al, 2011) though weaker weight reductions were observed compared to uncomplicated obesity (Danielsson et al, 2007). A recent study of both normal weight and obese CP patients showed that insulin resistance and altered gut hormone secretion are not exclusively a result of obesity but hypothalamic disruption caused by the tumor and/or its treatment (Roth et al, 2011b)
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