Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine

Zugno, Alexandra I.; Barcelos, Marcelo; Oliveira, Larissa Bertacchini de; Canever, Leila; Luca, Renata D. De; Fraga, Daiane B.; Matos, Maria Paula; Rezin, Gislaine T.; Scaini, Giselli; Búrigo, Márcio; Streck, Emílio L.; Quevedo, Joao L De

doi:10.1590/s1516-44462012000200009

Cited by 10 publications

(5 citation statements)

References 34 publications

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“…Moreover, Koro et al (2002) reported that olanzapine treatment is associated with a nearly fivefold increase in the prevalence of hyperlipidemia in contrast to the general population using a large database (which contains over 18,000 patients with schizophrenia). The effect of APPs on blood lipid profile in rodent models seems controversial, which showed no alteration ( Albaugh et al, 2006 ), or significant increase in triglyceride level after chronic olanzapine administration ( Skrede et al, 2012 ; Zugno et al, 2012 ). Yet, a recent animal study ( Horska et al, 2016 ) demonstrated that olanzapine is associated with hypertriglyceridemia and lowered LDL-C levels at the 8th day of olanzapine treatment, but these alterations could not persist after 8 weeks of olanzapine administration, and no significant alteration in blood lipid profiles was detected in later phase of olanzapine treatment.…”

Section: Discussionmentioning

confidence: 99%

The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance

et al. 2018

Front. Pharmacol.

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Olanzapine is a widely used atypical antipsychotic medication for treatment of schizophrenia and is often associated with serious metabolic abnormalities including weight gain and impaired glucose tolerance. These metabolic side effects are severe clinical problems but the underpinning mechanism remains poorly understood. Recently, growing evidence suggests that Wnt signaling pathway has a critical role in the pathogenesis of schizophrenia and molecular cascades of antipsychotics action, of which Wnt signaling pathway key effector TCF7L2 is strongly associated with glucose homeostasis. In this study, we aim to explore the characteristics of metabolic disturbance induced by olanzapine and to elucidate the role of TCF7L2 in this process. C57BL/6 mice were subject to olanzapine (4 mg/kg/day), or olanzapine plus metformin (150 mg/kg/day), or saline, respectively, for 8 weeks. Metabolic indices and TCF7L2 expression levels in liver, skeletal muscle, adipose, and pancreatic tissues were closely monitored. Olanzapine challenge induced remarkably increased body weight, fasting insulin, homeostasis model assessment-insulin resistance index, and TCF7L2 protein expression in liver, skeletal muscle, and adipose tissues. Notably, these effects could be effectively ameliorated by metformin. In addition, we found that olanzapine-induced body weight gain and insulin resistance actively influence the expression of TCF7L2 in liver and skeletal muscle, and elevated level of insulin determines the increased expression of TCF7L2 in adipose tissue. Our results demonstrate that TCF7L2 participates in olanzapine-induced metabolic disturbance, which presents a novel mechanism for olanzapine-induced metabolic disturbance and a potential therapeutic target to prevent the associated metabolic side effects.

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Section: Discussionmentioning

confidence: 99%

The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance

et al. 2018

Front. Pharmacol.

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“…A recent work from our group also described similar level of plasma leptin. 46 In both studies, weight gain might have been a consequence of the initial hypoleptinemia-dependent hyperphagia.…”

Section: Adverse Effects Of Aap Treatment On Rodentsmentioning

confidence: 95%

Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics

Volpato

Zugno

Quevedo

2013

Rev. Bras. Psiquiatr.

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Objective: Atypical antipsychotics (AAPs) promote obesity and insulin resistance. In this regard, the main objective of this study was to present potential mechanisms and evidence concerning side effects of atypical antipsychotics in humans and rodents. Method: A systematic review of the literature was performed using the MEDLINE database. We checked the references of selected articles, review articles, and books on the subject. Results: This review provides consistent results concerning the side effects of olanzapine (OL) and clozapine (CLZ), whereas we found conflicting results related to other AAPs. Most studies involving humans describe the effects on body weight, adiposity, lipid profile, and blood glucose levels. However, it seems difficult to identify an animal model replicating the wide range of changes observed in humans. Animal lineage, route of administration, dose, and duration of treatment should be carefully chosen for the replication of the findings in humans. Conclusions: Patients undergoing treatment with AAPs are at higher risk of developing adverse metabolic changes. This increased risk must be taken into account when making decisions about treatment. The influence of AAPs on multiple systems is certainly the cause of such effects. Specifically, muscarinic and histaminergic pathways seem to play important roles.

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“…In diet induced obese rodents, melatonin decreases levels of triglycerides and leptin resistance (Rios-Lugo et al, 2010). As with other antipsychotics, olanzapine increases levels of circulating triglycerides (Zugno et al, 2012). The efficacy of statins in schizophrenia is associated primarily with decreased triglycerides, suggesting that…”

Section: Leptinmentioning

confidence: 99%

Putative neuroprotective agents in neuropsychiatric disorders

Dodd

Maes

Anderson³

et al. 2013

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders.

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Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine

Abstract: These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.

Cited by 10 publications

References 34 publications

The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance

The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance

Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics

Putative neuroprotective agents in neuropsychiatric disorders

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