A model for antipsychotic-induced obesity in the male rat

Minet-Ringuet, Julie; Even, Patrick C.; Lacroix, Magali; Tomé, Daniel; Beaurepaire, Renaud de

doi:10.1007/s00213-006-0433-0

Cited by 63 publications

(38 citation statements)

References 31 publications

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“…Consistent with previous studies, olanzapine caused significant metabolic dysregulation, 22,24,31,[37][38][39][40][41][42][43] evident as elevated fasting glucose levels, insulin resistance (greater HOMA-IR values) and glucose intolerance in the IGTT. To our knowledge, we assessed the effects of metformin, rosiglitazone and glyburide on these metabolic side effects in rats for the first time.…”

Section: Discussionsupporting

confidence: 90%

Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced glucose dysregulation and insulin resistance in female rats

Boyda

Procyshyn²,

Tse

et al. 2012

J Psychiatry Neurosci

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Section: Discussionsupporting

confidence: 90%

Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced glucose dysregulation and insulin resistance in female rats

Boyda

Procyshyn²,

Tse

et al. 2012

J Psychiatry Neurosci

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“…One method to identify a clinical approach toward a weight management strategy is to better understand how SGAs might affect CNS feeding circuitry. Antipsychotic drugassociated weight gain in a male rodent model has been shown by Minet-Ringuet et al (2006); however, clozapine has not been found to induce weight gain or metabolic abnormalities in female rats, but was found to increase adiposity (Cooper et al, 2007). Although antipsychotic drugassociated weight gain in rodent models is in dispute in regard to sex, drug administration, diet, dose, and antipsychotic agents used, the use of OLZ in female rats has consistently been demonstrated to reproduce the weight gain, increased adiposity, and metabolic disturbances seen in patients (Albaugh et al, 2006;Arjona et al, 2004;Coccurello et al, 2006;Cooper et al, 2005;Cope et al, 2005;Goudie et al, 2002;Raskind et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Wallingford

Sinnayah

Bymaster

et al. 2008

Neuropsychopharmacol

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Olanzapine (OLZ), one of the second-generation atypical antipsychotics (SGAs), has shown relative advantages in patient adherence and outcomes. However, OLZ has also been associated with a higher incidence of weight gain than most other SGAs. Excessive weight gain may in turn contribute to long-term health concerns for some individuals. Zonisamide (ZNS), a medication approved in the United States as an adjunct in the management of epilepsy, has a diverse pharmacological profile, including sodium channel blockade, monoamine enhancement, and inhibition of carbonic anhydrase. ZNS has also been reported to cause weight loss in both humans and rodents. We hypothesized that this profile might be beneficial when co-administered with OLZ. To test this hypothesis, we evaluated the effects of OLZ on body weight, as well as the pathways known to regulate feeding behavior and arousal in the Sprague-Dawley rat. As indicated via c-Fos expression, we found an OLZ-induced activation in the nucleus accumbens and orexin neurons in the lateral hypothalamus. An OLZ-associated development of hyperphagia, weight gain and elevated blood glucose in the rat was also found. These outcomes were attenuated and reversed in the presence of concomitant ZNS. These results suggest the hypothesis that ZNS may effectively treat or prevent weight gain or metabolic changes associated with the SGAs. Future studies of this combination in patients through appropriately designed human clinical studies are encouraged.

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“…Our results confirm previous observations of an increased fat deposition in rats under olanzapine treatment. 20,30 And they shed more light on the mechanisms involved.…”

Section: Discussionmentioning

confidence: 99%

“…Food intake increased in olanzapinetreated animals without reaching significance (data not shown); the increase in food intake was parallel to the increase in body weight, similar to the results reported in our previously published experiments using the same technique. 20 Lipolytic and antilipolytic activities in adipocytes from control and antipsychotic-treated rats Basal lipolysis was unmodified in adipocytes isolated from the INWAT of antipsychotic-treated rats when compared to control. However, the dose-dependent stimulation of lipolysis induced by the b-adrenergic agonist isoprenaline was significantly weaker in the olanzapine-treated group than in the control group (Figure 2).…”

Section: Adiposity At the End Of Treatmentsmentioning

confidence: 99%

“…To that purpose, we used a rat model of antipsychoticinduced obesity that we recently developed, 20 and which consists in feeding male rats with a diet (called P14L) enriched in carbohydrates and impoverished in proteins to a level comparable to that observed in the 'human diet' (31% fat energy, 56% glucid energy, 14% protein energy, whereas rats spontaneously eat high amounts of protein energy (35%) and small amounts of carbohydrate energy (15%)). We measured and compared the effect of a classical (haloperidol) and atypical antipsychotics (olanzapine and ziprasidone) on lipolysis and glucose transport in white adipocytes.…”

Section: Introductionmentioning

confidence: 99%

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Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment

et al. 2007

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Although antipsychotics are established drugs in schizophrenia treatment, they are admittedly known to induce side effects favoring the onset of obesity and worsening its complications. Despite potential involvement of histamine receptor antagonism, or of other neurotransmitter systems, the mechanism by which antipsychotic drugs increase body weight is not elucidated. The aim of the present study was to investigate whether chronic antipsychotic treatments can directly alter the regulation of two main functions of white adipose tissue: lipolysis and glucose utilization. The influence of a classical antipsychotic (haloperidol) was compared to that of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (ziprasidone). Cell size, lipolytic capacity and glucose transport activity were determined in white adipocytes of rats subjected to 5-week oral treatment with these antipsychotics. Gene expression of adipocyte proteins involved in glucose transport or fat storage and mobilization, such as glucose transporters (GLUT1 and GLUT4), leptin, matrix metallo-proteinase-9 (MMP9), hormone-sensitive lipase (HSL) and fatty acid synthase (FAS) was also evaluated. Adipocytes from chronic olanzapine-treated rats exhibited decreased lipolytic activity, lowered HSL expression and increased FAS expression. These changes were concomitant to enlarged fat deposition and adipocyte size. Alterations were observed in adipocytes from olanzapinetreated rats whereas the other antipsychotics did not induce any notable disorder. Our results therefore show evidence of an effect of chronic antipsychotic treatment on rat adipocyte metabolism. Thus, impairment of fat cell lipolysis should be considered as a side effect of certain antipsychotics, leading, along with the already documented hyperphagia, to the excessive weight gain observed in patients under prolonged treatment.

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A model for antipsychotic-induced obesity in the male rat

Abstract: This study shows that a rat model of obesity induced by antipsychotics can be created under specific conditions of drug administration, diet, and dose.

Cited by 63 publications

References 31 publications

Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced glucose dysregulation and insulin resistance in female rats

Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced glucose dysregulation and insulin resistance in female rats

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment

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