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Effects of metformin on olanzapine induced weight gain in male wistar rats: the change of hypothalamic neurohormones involved in body weight regulation

Kurt, Gizem
Obesity, resulting from the extreme weight gain, is one of the biggest health problems nowadays because it causes disruption of the metabolism and metabolic problems, including type 2 diabetes mellitus, dyslipidemia and cardiovascular disease. Atypical (second generation) antipsychotic drugs, which are highly in use, have adverse effects including weight gain. Ongoing researches for the treatment of antipsychotics induced-weight gain are present and one of the promising agents is metformin, an anti-diabetic drug. However, hypothalamic targets and cellular action mechanisms of metformin in the antipsychotic-treated brain is still unknown. The main regulator of the appetite, weight balance and energy homeostasis is the hypothalamus, and hypothalamic neurohormones; proopiomelanocortin (POMC), anorexigenic, and neuropeptide Y (NPY), orexigenic, are potent. The aim of this study was to investigate the underlying hypothalamic mechanisms of the metformin treatment of atypical antipsychotic olanzapine-induced weight gain in male Wistar rats. Our hypothesis was the treatment of olanzapine increases the orexigenic peptide and decreases the anorexigenic peptide expression levels in the hypothalamus whereas metformin which can pass the brain blood barrier (BBB) might reverse those possible effects. Our results indicated that POMC expression in the hypothalamus decreased in all olanzapine groups regardless of the metformin administration. In addition, metformin could not fully restore the significantly increased hypothalamic NPY expression resulting from olanzapine treatment.