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• W2792989874 abstract "Apelin is a peptide ligand of the G-protein-coupled receptor APJ and exhibits anti-diabetes and anti-heart failure activities. However, short serum half-life of the apelin peptide limits its potential clinical applications. This study aimed to develop a long-acting apelin analog.To extend apelin's in vivo half-life, we made a recombinant protein by fusing the IgG Fc fragment to apelin-13 (Fc-apelin-13), conducted pharmacokinetics studies in mice, and determined in vitro biological activities in suppressing cyclic adenosine monophosphate and activating extracellular signal-regulated kinase signalling by reporter assays. We investigated the effects of Fc-apelin-13 on food intake, body weight, fasting blood glucose and insulin levels, glucose tolerance test, hepatic steatosis, and cardiac function and fibrosis by subcutaneous administration of Fc-apelin-13 in diet-induced obese mice for 4 weeks.The estimated half-life of Fc-apelin-13 in blood was approximately 33 hours. Reporter assays showed that Fc-apelin-13 was active in suppressing cyclic adenosine monophosphate response element and activating serum response element activities. Four weeks of Fc-apelin-13 treatment in obese mice did not affect food intake and body weight, but resulted in a significant improvement of glucose tolerance, and a decrease in hepatic steatosis and fibrosis, as well as in serum alanine transaminase levels. Moreover, cardiac stroke volume and output were increased and cardiac fibrosis was decreased in the treated mice.Fc-apelin-13 fusion protein has an extended in vivo half-life and exerts multiple benefits on obese mice with respect to the improvement of glucose disposal, amelioration of liver steatosis and heart fibrosis, and increase of cardiac output. Hence, Fc-apelin-13 is potentially a therapeutic for obesity-associated disease conditions." @default.
• W2792989874 created "2018-03-29" @default.
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• W2792989874 date "2018-03-25" @default.
• W2792989874 modified "2023-09-24" @default.
• W2792989874 title "Hepatic and cardiac beneficial effects of a long-acting Fc-apelin fusion protein in diet-induced obese mice" @default.
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• W2792989874 doi "https://doi.org/10.1002/dmrr.2997" @default.
• W2792989874 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29577579" @default.
• W2792989874 hasPublicationYear "2018" @default.
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