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Chronic treatment with olanzapine increases adiposity by changing fuel substrate and causes desensitization of the acute metabolic side effects
- 作者:Elodie M. Girault (1)
Bruno Guigas (4) (5) Anneke Alkemade (2) Ewout Foppen (1) (2) Mari?tte T. Ackermans (3) Susanne E. la Fleur (2) Eric Fliers (2) Andries Kalsbeek (1) (2)
- 关键词:Body fat composition ; Energy expenditure ; Glucose metabolism ; Locomotor activity ; Respiratory exchange ratio ; Food intake
- 刊名:Naunyn-Schmiedeberg's Archives of Pharmacology
- 出版年:2014
- 出版时间:February 2014
- 年:2014
- 卷:387
- 期:2
- 页码:185-195
- 全文大小:475 KB
- 作者单位:Elodie M. Girault (1)
Bruno Guigas (4) (5) Anneke Alkemade (2) Ewout Foppen (1) (2) Mari?tte T. Ackermans (3) Susanne E. la Fleur (2) Eric Fliers (2) Andries Kalsbeek (1) (2)
1. Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands 4. Department of Molecular Cell Biology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands 5. Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands 2. Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands 3. Laboratory of Endocrinology, Department of Clinical Chemistry, Academic Medical Center (AMC), University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands
- ISSN:1432-1912
文摘
Atypical antipsychotic drugs such as olanzapine induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these metabolic side-effects are unknown at the moment. In this study, we investigated the metabolic changes induced by a chronic treatment, as well as the influence of a preceding chronic treatment on the acute effects of olanzapine on glucose metabolism. The effect of chronic olanzapine treatment (±6.5?mg/kg/day, administered via drinking water) on body weight, locomotor activity, body temperature, fat distribution and energy expenditure was investigated in male rats. After 5?weeks, the animals received an acute olanzapine challenge (intragastric, IG) at 3?mg/kg/h during 160?min to investigate the acute effects of olanzapine on glucose metabolism. Chronic olanzapine-treated animals showed a slight decrease in nocturnal body temperature, and increased perirenal fat pad weights as well as plasma leptin. In addition, chronic olanzapine-treated animals showed hyperinsulinaemia with unchanged blood glucose concentrations. The acute challenge with IG olanzapine elevated blood glucose levels and endogenous glucose production in control animals, but not in chronic olanzapine-pre-treated rats. Chronic olanzapine-treated animals also showed reduced locomotor activity and a higher respiratory exchange ratio. Thus, chronic treatment with olanzapine in rats causes desensitization to its acute effects on glucose metabolism but promotes adiposity probably due to a shift from lipids to carbohydrates as an energy source. Chronic exposure to olanzapine changes body fat distribution and insulin sensitivity in an unfavourable direction, but it is still unclear what the primary mechanism is.
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