Potent synergistic effects of dulaglutide and food restriction in prevention of olanzapine-induced metabolic adverse effects in a rodent model
Language English Country France Media print-electronic
Document type Journal Article
PubMed
38805968
DOI
10.1016/j.biopha.2024.116763
PII: S0753-3322(24)00647-4
Knihovny.cz E-resources
- Keywords
- Antipsychotic, GLP-1 receptor agonist, Olanzapine, metabolic adverse effects, Schizophrenia,
- MeSH
- Glucagon-Like Peptide-1 Receptor Agonists MeSH
- Antipsychotic Agents pharmacology adverse effects MeSH
- Benzodiazepines pharmacology adverse effects MeSH
- Glucagon-Like Peptides * analogs & derivatives pharmacology MeSH
- Weight Gain drug effects MeSH
- Immunoglobulin Fc Fragments * pharmacology MeSH
- Caloric Restriction methods MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Olanzapine * pharmacology adverse effects MeSH
- Rats, Sprague-Dawley * MeSH
- Eating drug effects MeSH
- Glucagon-Like Peptide-1 Receptor metabolism MeSH
- Recombinant Fusion Proteins * pharmacology MeSH
- Body Weight drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Glucagon-Like Peptide-1 Receptor Agonists MeSH
- Antipsychotic Agents MeSH
- Benzodiazepines MeSH
- dulaglutide MeSH Browser
- Glucagon-Like Peptides * MeSH
- Immunoglobulin Fc Fragments * MeSH
- Olanzapine * MeSH
- Glucagon-Like Peptide-1 Receptor MeSH
- Recombinant Fusion Proteins * MeSH
BACKGROUND: Antipsychotics are indispensable in the treatment of severe mental illneses, however adverse metabolic effects including diabetes, weight gain, dyslipidemia, and related cardiovascular morbidity are common, and current pharmacological strategies for their management are unsatisfactory. Glucagon-like 1 peptide receptor agonists (GLP-1 RAs) are approved for the treatment of type 2 diabetes and obesity hold promise for the management of antipsychotic-associated adverse metabolic effects. METHODS: To characterize the molecular effects and identify biomarkers for GLP-1 RA preventive treatment, Sprague-Dawley female rats were treated with long-acting formulations of the antipsychotic olanzapine and the GLP-1 RA dulaglutide for 8 days. A pair-feeding protocol evaluated the combined effects of dulaglutide and food restriction on an olanzapine-induced metabolic phenotype. Body weight and food consumption were recorded. Biochemical analysis included a lipid profile, a spectrum of gastrointestinal and adipose tissue-derived hormones, and fibroblast growth factor 21 serum levels. RESULTS: Olanzapine induced hyperphagia, weight gain, increased serum triglycerides and HDL cholesterol. Food restriction affected the OLA-induced phenotype but not serum markers. Dulaglutide led to a modest decrease in food intake, with no effect on weight gain, and did not reverse the OLA-induced changes in serum lipid parameters. Concomitant dulaglutide and food restriction resulted in weight loss, decreased feed efficiency, and lower total and HDL cholesterol. CONCLUSIONS: A combined strategy of dulaglutide and food restriction manifested a massive synergistic benefit. GLP-1RAs represent a promising strategy and deserve thorough future research. Our findings underline the potential importance of lifestyle intervention in addition to GLP-1 RA treatment.
Department of Pharmacology and Toxicology Faculty of Pharmacy Masaryk University Brno Czech Republic
Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic
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