Olanzapine induces SREBP-1-related adipogenesis in 3T3-L1 cells

Yang, Li-Hung; Chen, Tzer-Ming; Yu, Sung-Tsai; Chen, Yen‐Hui

doi:10.1016/j.phrs.2007.05.007

Cited by 105 publications

(92 citation statements)

References 27 publications

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“…Consistently with this, a previous study reported an upregulation of srebp-1 and SREBP-1-related adipogenesis in the 3T3-L1 adipocyte cell line (Yang et al 2007). However, an in vivo study has reported that, following one i.p.…”

Section: Discussionsupporting

confidence: 80%

“…SREBP-1 is known as a key regulator of fatty acid synthesis and a molecular link between lipid metabolism, insulin action and obesity at the gene regulatory level (Kotzka & Muller-Wieland 2004), while SREBP-2 is the main regulator of cholesterol metabolism (Shimano 2001). Clozapine and olanzapine induce upregulated expression of SREBPs and target genes in several cell lines, primary rat hepatocytes and in vivo 2-week treatment study (Fernø et al 2005;Skrede et al 2012;Yang et al 2007). However, in contrast to the findings, acute studies in female rats found that a single intraperitoneal (i.p.)…”

Section: Introductionmentioning

confidence: 99%

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Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats

et al. 2015

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. (2015). Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats. Life Sciences, Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats AbstractAims Second-generation antipsychotic drugs (SGAs) have a high risk for serious metabolic side-effects including dyslipidemia. This study aimed to investigate the acute effects of oral olanzapine treatment on the expression of genes for fatty acid and cholesterol biosynthesis in rats. Main methods Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg, equivalent to a human clinical dose of 10 mg) via selfadministration aimed to measure pharmacokinetics. Based on the pharmacokinetic analysis, the acute effects of olanzapine on sterol regulatory element binding protein (SREBP)-related fatty acid/cholesterol metabolism genes were investigated in the liver and perirenal white adipose tissue (WAT) by Real-time quantitative PCR. Key findings A pharmacokinetic analysis demonstrated that the maximum concentration of olanzapine in plasma (Cmax) occurred at 6 h with a peak concentration of 276.5 ng/ml after a single oral treatment and with a plasma elimination half-life of 3.5 h after peak. The mRNA expression of SREBP-2 and target genes for cholesterol synthesis and transport was increased 1.9 8.8 fold compared with the control at 6 h after olanzapine administration but returned to basal level at 12 h post-treatment, while the increased mRNA expression of SREBP-1c and its targeted fatty acid-related genes appeared at both 6 h and 12 h post-treatment. Significance The present study provided evidence that olanzapine at a clinically-relevant dose caused abnormal expression of genes involved in lipid metabolism in the liver and WAT. These results suggest that olanzapine may cause dyslipidemia side-effects through direct effects on lipid biosynthesis and efflux genes associated with SREBP-stimulated transcriptional changes. Disciplines Medicine and Health Sciences Publication DetailsLiu, X., Deng, C., Cao, S., Gong, J., Wang, B. & Hu, C. (2015). Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats. Life Sciences, 128 72-78. Second-generation antipsychotic drugs (SGAs) have a high risk for serious metabolic sideeffects including dyslipidemia. This study aimed to investigate the acute effects of oral olanzapine treatment on the expression of genes for fatty acid and cholesterol biosynthesis in rats. Main methods:Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg, equivalent to human clinical dose of 10 mg) via self-administration aimed to measure pharmacokinetics.Based on the pharmacokinetic analysis, the acute effects of olanzapine on SREBP-related fatty acid/cholesterol metabolism genes were investigated in the liver and perirenal white adipose tissue (WAT) by Real-time quantitative PCR. Key findings:A pharmacokinetic analysis demonstrated that ...

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats

et al. 2015

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“…Using Olanzapine is preferred than older antipsychotic agents due to its less side effects on extra pyramidal tract [1,2] .It is widely prescribed for the treatment of schizophrenia [3] . It is effective against the positive and the negative symptoms of schizophrenia [4] .…”

Section: Introductionmentioning

confidence: 99%

Histological Study of the Effects of Olanzapine on the Liver of Adult Male Albino Rat with and without Vitamin C

Elbakary

2017

Egyptian Journal of Histology

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Introduction: Olanzapine is an atypical antipsychotic drug widely used in treatment of schizophrenia for prolonged time. Aim of the work: The present study was carried out to evaluate the effect of olanzapine on the liver and the possible protective effect of vitamin C. Material and Methods: Forty adult male albino rats were used in this work. They were divided into: Group I as a control, group II was given Olanzapine (2mg/kg B. wt. orally once daily) for one month, group III was given Olanzapine (at the same previous dose) plus vitamin C (15 mg /Kg. B. wt of orally once daily) for one month and group IV was given only vitamin C (for the same dose and period of the previous group). At the end of the experiment, liver specimens were processed for histological study by light and electron microscopes. Also blood samples were collected for estimation of liver enzymes. Result: Significant increase in the level of liver enzymes was observed in Olanzapine treated group. While the microscopic examination of the liver sections of this group revealed several histological changes including, dilatation and congestion of central veins and blood sinusoids, inflammatory cellular infiltration in the portal areas and cytoplasmic vacuolation of hepatocytes that present mainly around the central veins. Mitochondrial degeneration, bile ducts dilatation and excessive deposition of lipid droplets were also observed. These changes were ameliorated by vitamin C administration. Conclusion: Results of this experimental work revealed that administration of vitamin C greatly reduced the histological alterations induced by Olanzapine, suggesting that vitamin C has a protective effect on the liver.

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“…11 Similarly, olanzapine induced adipogenesis in 3T3-L1 preadipocytes, probably through activation of the sterol regulatory element-binding protein-1 regulatory pathway. 12 A recent study, in which olanzapine, ziprasidone and haloperidol were tested on animal adipocytes, showed that only olanzapine administration decreased lipolysis in adipocytes, as well as induced a gene fatty acid synthase overexpression and a gene hormonesensitive lipase repression that resulted in a significant fat accumulation in rats. 13 In light of these considerations, it could be concluded that obesity event associated with administration of different APDs could be enhanced by several pathways.…”

Section: Introductionmentioning

confidence: 99%

Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-β

et al. 2009

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Atypical antipsychotics (APDs) are currently used in clinical practice for a variety of mental disorders such as schizophrenia, bipolar disorder and severe behavioral disturbances. A well-known disadvantage of using these compounds is a propensity for weight gain, resulting frequently in obesity. The mechanisms underlying pharmacologically induced weight gain are still controversial. The objective of this study was to evaluate in vitro the effects of different APDs on adipogenic events in cultured human pre-adipocytes and in rat muscle-derived stem cells (MDSCs), aiming to identify a common intracellular event contributable to these drugs. Culture behavior was evaluated in terms of cell proliferation, lipid accumulation, gene expression and morphological features. Results indicate that APDs influence adipogenic events through changes in the differentiation and proliferation of preadipocytes and MDSCs that are brought on by protein kinase C-b (PKC-b) activation. These data identify a signaling route that could be a potential target of pharmacological approaches for preventing the weight gain associated with APD treatment.

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Olanzapine induces SREBP-1-related adipogenesis in 3T3-L1 cells

Cited by 105 publications

References 27 publications

Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats

Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats

Histological Study of the Effects of Olanzapine on the Liver of Adult Male Albino Rat with and without Vitamin C

Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-β

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