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Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin
Changhua Hu
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8889-711X
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Pharmacology and Toxicology.
Background Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.
Methods To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks.
Results Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by co-treatment with O+B. Conclusions Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.
Keywords
simvastatin, olanzapine, brown adipose tissue, body weight gain, dyslipidemia
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Editorial decision: Major revision
On 27 May, 2020
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Received 29 Apr, 2020
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On 25 Mar, 2020
Review #2 received
Received 11 Mar, 2020
Review #1 received
Received 20 Jan, 2020
Reviewer #2 agreed
On 09 Jan, 2020
Reviewers invited
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Reviewer #1 agreed
On 06 Jan, 2020
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On 02 Dec, 2019
Submission checks complete
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This preprint is under consideration at BMC Pharmacology and Toxicology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin
Changhua Hu
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8889-711X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 4
Posted 17 Jun, 2020
Published
On 30 Jun, 2020
No community comments so far
Editorial decision: Accept
On 17 Jun, 2020
Editor assigned
On 15 Jun, 2020
Submission checks complete
On 14 Jun, 2020
Editor invited
On 14 Jun, 2020
No comments provided
Editorial decision: Minor revision
On 10 Jun, 2020
Editor assigned
On 07 Jun, 2020
Submission checks complete
On 06 Jun, 2020
Editor invited
On 06 Jun, 2020
No comments provided
Editorial decision: Major revision
On 27 May, 2020
Review #2 received
Received 22 May, 2020
Review #1 received
Received 29 Apr, 2020
Reviewers invited
Invitations sent on 28 Apr, 2020
Reviewer #1 agreed
On 28 Apr, 2020
Reviewer #2 agreed
On 28 Apr, 2020
Editor assigned
On 26 Apr, 2020
Submission checks complete
On 25 Apr, 2020
Editor invited
On 25 Apr, 2020
No comments provided
Editorial decision: Major revision
On 25 Mar, 2020
Review #2 received
Received 11 Mar, 2020
Review #1 received
Received 20 Jan, 2020
Reviewer #2 agreed
On 09 Jan, 2020
Reviewers invited
Invitations sent on 06 Jan, 2020
Reviewer #1 agreed
On 06 Jan, 2020
Editor assigned
On 02 Dec, 2019
Submission checks complete
On 01 Dec, 2019
Editor invited
On 01 Dec, 2019
First submitted
On 29 Nov, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Pharmacology and Toxicology.
Background Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.
Methods To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks.
Results Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by co-treatment with O+B. Conclusions Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.
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