Alterations of hypothalamic neuropeptides involved in food intake and appetite in olanzapine monotherapy

Sezlev, Deniz
The mechanism of weight gain due to treatment with olanzapine, a serotonin receptor antagonist, has not been fully understood. Weight gain and food intake are under the control of neuropeptides/hormones, POMC (proopiomelanocortin), CART (cocaine and amphetamine regulated transcript), AgRP (Agouti-related peptide) and NPY (neuropeptide Y) that are synthesized and secreted from the arcuate nucleus (ARC) of hypothalamus. In this study, the altereration of the ARC neuropeptide/hormone levels both in humans and rats were determined as one of the weight gain mechanism. To examine olanzapine’s weight gain effects, male first attack psychotic patients (pre-treatment), were hospitalized and treated for 4 -weeks (post-treatment), (n = 22), and healthy control group (n = 26) were included to the study. Case-control association design was used to analyze the changes in body mass index (BMI), peripheral leptin and the ARC neuropeptides levels. In patients, after 4-weeks of the olanzapine treatment; BMI and the waist circumference were significantly increased with average weight gain of 4.33 kg. In pre-treatment group, NPY levels were significantly lower while α-MSH, the anorexigenic product of POMC levels were significantly higher vs. control. At post-treatment, both leptin and NPY levels were significantly increased but the CART levels did not change. To further understand the underlying mechanism of olanzapine induced weight gain, the drug was orally administrated to 10 healthy male Wistar rats to analyze both the hypotalamic gene expression and peripheral levels of those candidate neuropeptides. In rats food consumption was increased and hypotalamic mRNA levels of NPY, AgRP and POMC were decreased while CART levels did not show any alteration. Consistent with the expression data, circulating levels of NPY, AgRP and α-MSH decreased significantly but CART levels were also reduced unexpectedly. In conclusion, it may be presumed that the antagonistic effect of olanzapine on the ARC neurons might be the basis for a disregulation of the neurohormones secretion which may cause weight gain in the treated psychotic patients.
Citation Formats
D. Sezlev, “Alterations of hypothalamic neuropeptides involved in food intake and appetite in olanzapine monotherapy,” M.S. - Master of Science, Middle East Technical University, 2012.