Abstract
Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance.
Highlights
Schizophrenia is a chronic and debilitating mental illness
The development of weight gain and metabolic adverse effects could further lead to increased morbidity and mortality, along with poor compliance to antipsychotic medications for patients with schizophrenia
Given its well-known biological activity in regulating glucose and lipid metabolism, we hypothesized that chromium mobilization may play a role in atypical antipsychotics-accompanied weight gain and metabolic disturbance
Summary
Schizophrenia is a chronic and debilitating mental illness. Its long-lasting health, social, and financial burdens on humans are rising, due to its high global prevalence. The development of weight gain and metabolic adverse effects could further lead to increased morbidity and mortality, along with poor compliance to antipsychotic medications for patients with schizophrenia. A better understanding of atypical antipsychotics-accompanied weight gain and metabolic disturbance, as well as the identification of prevention and/or treatment options is believed to have more clinical benefits for patients with schizophrenia. Metabolism-improving agents, such as metformin, liraglutide, berberine, green tea, and melatonin, show beneficial effects as well [23,24,25,26,27,28] These phenomena highlight the feasibility of metabolic regulators’ ability to combat atypical antipsychotics-accompanied weight gain and metabolic disturbance. Given its well-known biological activity in regulating glucose and lipid metabolism, we hypothesized that chromium mobilization may play a role in atypical antipsychotics-accompanied weight gain and metabolic disturbance. FigurFeigu2.re 2.OOllaannzzaappiinneecacuaseudseadmeatabmoleitcadbiostluicrbadnicset.uArbt athneceen. d ofAtthetehxepeerinmdenotsf, sethruemesxapmeprliems ents, serumwesraemspulbejescwtederetosuanbajelycsteesdftoor athnealmyseeassufroermtehnetmofeaasspuarretmateenatmoifnoatsrpaanrstfaertaesaem(AinSoTt)r(aAn)s,faelraansiene(AST) (A), aalmanininoetraanmsfienroastera(nAsLfTer)a(sBe),(tAriLgTly)ce(rBid),etsri(gCl)y, ctoetraildcehso(lCes)t,ertoolta(Dl c),hfoalsetisntgergollu(cDos)e, f(aEs),tianngd ginlusucloinse (E), and in(Fs)u. lTinhe(Fv)a. lTuheeovf aHluome oeof sHtaosmis eMoostdaeslisAMsseosdseml eAnst-sIensssumlinenRt-eIsnisstuanlicneR(HesOisMtaAn-cIeR()HisOdMepAic-tIeRd)iins d(Ge)p.icted in (G)(H. ()HP)rPotreoitnesinwsewreereexterxatcrtaedctefrdomfrotmhethexeceisxecdisleivdelrivtiesrsutiesssuanesdasnudbjseuctbejdecttoedWteostWerenstbelronttibnlgotwtinitgh with indicainteddicaatnetdibaondtiibeosd. iRese.pRreepsreensteanttiavteivbelboltostasraereshshoowwnn,,aanndd tthheeqquuaanntittiatatitvievedadtaataareardeepdiecpteidct.e*dp .
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