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Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice

Liraglutide, a glucagon-like peptide-1 analog, has beneficial metabolic effects in patients with type 2 diabetes and obesity. Although the high efficacy of liraglutide as an anti-diabetic and anti-obesity drug is well known, liraglutide-induced metabolic alterations in diverse tissues remain largely...

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Autores principales: Park, Seokjae, Oh, Sungjoon, Kim, Eun-Kyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730228/
https://www.ncbi.nlm.nih.gov/pubmed/36356900
http://dx.doi.org/10.1016/j.jbc.2022.102682
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author Park, Seokjae
Oh, Sungjoon
Kim, Eun-Kyoung
author_facet Park, Seokjae
Oh, Sungjoon
Kim, Eun-Kyoung
author_sort Park, Seokjae
collection PubMed
description Liraglutide, a glucagon-like peptide-1 analog, has beneficial metabolic effects in patients with type 2 diabetes and obesity. Although the high efficacy of liraglutide as an anti-diabetic and anti-obesity drug is well known, liraglutide-induced metabolic alterations in diverse tissues remain largely unexplored. Here, we report the changes in metabolic profiles induced by a 2-week subcutaneous injection of liraglutide in diet-induced obese mice fed a high-fat diet for 8 weeks. Our comprehensive metabolomic analyses of the hypothalamus, plasma, liver, and skeletal muscle showed that liraglutide intervention led to various metabolic alterations in comparison with diet-induced obese or nonobese mice. We found that liraglutide remarkably coordinated not only fatty acid metabolism in the hypothalamus and skeletal muscle but also amino acid and carbohydrate metabolism in plasma and liver. Comparative analyses of metabolite dynamics revealed that liraglutide rewired intertissue metabolic correlations. Our study points to a previously unappreciated metabolic alteration by liraglutide in several tissues, which may underlie its therapeutic effects within and across the tissues.
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spelling pubmed-97302282022-12-12 Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice Park, Seokjae Oh, Sungjoon Kim, Eun-Kyoung J Biol Chem Research Article Liraglutide, a glucagon-like peptide-1 analog, has beneficial metabolic effects in patients with type 2 diabetes and obesity. Although the high efficacy of liraglutide as an anti-diabetic and anti-obesity drug is well known, liraglutide-induced metabolic alterations in diverse tissues remain largely unexplored. Here, we report the changes in metabolic profiles induced by a 2-week subcutaneous injection of liraglutide in diet-induced obese mice fed a high-fat diet for 8 weeks. Our comprehensive metabolomic analyses of the hypothalamus, plasma, liver, and skeletal muscle showed that liraglutide intervention led to various metabolic alterations in comparison with diet-induced obese or nonobese mice. We found that liraglutide remarkably coordinated not only fatty acid metabolism in the hypothalamus and skeletal muscle but also amino acid and carbohydrate metabolism in plasma and liver. Comparative analyses of metabolite dynamics revealed that liraglutide rewired intertissue metabolic correlations. Our study points to a previously unappreciated metabolic alteration by liraglutide in several tissues, which may underlie its therapeutic effects within and across the tissues. American Society for Biochemistry and Molecular Biology 2022-11-07 /pmc/articles/PMC9730228/ /pubmed/36356900 http://dx.doi.org/10.1016/j.jbc.2022.102682 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Park, Seokjae
Oh, Sungjoon
Kim, Eun-Kyoung
Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice
title Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice
title_full Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice
title_fullStr Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice
title_full_unstemmed Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice
title_short Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice
title_sort glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730228/
https://www.ncbi.nlm.nih.gov/pubmed/36356900
http://dx.doi.org/10.1016/j.jbc.2022.102682
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