The Role of Ghrelin in Weight Gain and Growth in Epileptic Children Using Valproate

Abstract

Ghrelin is a major hormone, regulating the energy balance of the body. Weight gain is a significant side effect of valproic acid, which has not been clearly identified pathogenetically. The aim of this study was to investigate the effect of valproic acid on ghrelin and its potential effects on weight gain and growth. Each patient and control group consisted of 35 children aged 3 to 15 years. Fasting serum glucose, insulin, C-peptide, leptin, ghrelin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels were measured in patients treated with valproic acid before and at month 6 of treatment. A significant increase in body weight, body mass index, height, and height standard deviation scores was observed in all patients after 6 months of treatment. Significant increases in growth velocity and weight gain were observed in the patient group compared with controls at 6 months of therapy. A significant increase in serum ghrelin levels (P < .01) was detected at the same time in the study group. A negative correlation of ghrelin with insulin-like growth factor-1 and insulin-like growth factor binding protein-3 was detected. Serum ghrelin levels were significantly increased (P < .05), and insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were significantly decreased (P < .01 and P < .05, respectively) in the prepubertal group at 6 months of treatment, but no significant change was observed in the pubertal group. Consequently, ghrelin levels significantly increase in the prepubertal children treated with valproic acid. The weight gain in using valproic acid may be associated with the increase in ghrelin level in the early treatment period.

Interictal ghrelin levels in adult patients with epilepsy

“…This is somewhat in contrast to previous studies, since for instance ghrelin levels were increased in children treated with VPA in prepubertal (but not in pubertal) status. 28,29 Yet, Greco et al, 30 found lower ghrelin levels in pubertal subjects who significantly gained weight during VPA treatment. However, if very young prepubertal children were considered separately, total ghrelin levels were decreased prior to/ independent of a consistent weight gain while on CBZ and VPA.…”

Plasma leptin, neuropeptide Y, ghrelin, and adiponectin levels and carotid artery intima media thickness in epileptic children treated with valproate

“…Greco et al [13] noted that serum adiponectin and ghrelin levels were significantly lower in adult patients with VPA-associated obesity than those in controls. Güngör et al [19] conducted a study including 35 patients treated with VPA and 35 volunteers aged 3 to 15 years, which showed that serum ghrelin levels were significantly higher in those treated with VPA than those in controls. In the current study, serum ghrelin levels did not significantly change over time.…”

Inactivation of the Constitutively Active Ghrelin Receptor Attenuates Limbic Seizure Activity in Rodents

“…Recently ghrelin has been investigated with respect to its potential role in epilepsy. Data from human studies in this area are conflicting, with some studies concluding either increased [15,16] or decreased [17][18][19][20][21][22] plasma levels of ghrelin in epileptic patients. Rodent studies are more consistent, with the majority of studies indicating that ghrelin shows an anticonvulsant action in different models [10,[23][24][25], but its mechanism of action is unknown.…”