AM-879, a PPARy non-agonist and Ser273 phosphorylation blocker, promotes insulin sensitivity without adverse effects in mice.

Autor:	Terra MF; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil.; Post Graduate Program in Functional and Molecular Biology, Institute of Biology, State University of Campinas (Unicamp), Campinas, Brazil., García-Arévalo M; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil., Avelino TM; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil.; Post Graduate Program in Pharmacological Science, State University of Campinas (Unicamp), Campinas, Brazil., Degaki KY; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil., Malospirito CC; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil.; Post Graduate Program in Functional and Molecular Biology, Institute of Biology, State University of Campinas (Unicamp), Campinas, Brazil., de Carvalho M; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil.; Brazilian Synchrotron Light Laboratory (LNLS), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Torres FR; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil., Saito Â; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil., Figueira ACM; Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil.
Jazyk:	angličtina
Zdroj:	Metabolism open [Metabol Open] 2022 Dec 21; Vol. 17, pp. 100221. Date of Electronic Publication: 2022 Dec 21 (Print Publication: 2023).
DOI:	10.1016/j.metop.2022.100221
Abstrakt:	Obesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the in vivo effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose. At lower doses, this ligand decreased BAT, increased leptin and Crh expression. However, at a higher dose, it promoted improvement on insulin sensitivity, ameliorates expression of metabolism-related genes, decreased the expression of genes related to liver toxicity, maintaining body weight and adipocyte size. These results present a new lead molecule to ameliorates insulin resistance and confirm AM-879 as a PPARγ non-agonist which blocks Ser273 phosphorylation as a good strategy to modulate insulin sensitivity without developing the adverse effects promoted by PPARγ full agonists. (© 2022 Published by Elsevier Inc.)
Databáze:	MEDLINE
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