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PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates

PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mech...

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Autores principales: Thompson, W. Clayton, Zhou, Yingjiang, Talukdar, Saswata, Musante, Cynthia J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4954843/
https://www.ncbi.nlm.nih.gov/pubmed/27405817
http://dx.doi.org/10.1007/s10928-016-9481-1
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author Thompson, W. Clayton
Zhou, Yingjiang
Talukdar, Saswata
Musante, Cynthia J.
author_facet Thompson, W. Clayton
Zhou, Yingjiang
Talukdar, Saswata
Musante, Cynthia J.
author_sort Thompson, W. Clayton
collection PubMed
description PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mechanisms of action remain unclear. In particular, there have been conflicting reports on the degree to which FGF21-induced weight loss in non-human primates is attributable to a decrease in food intake versus an increase in energy expenditure. Here, we present a semi-mechanistic mathematical model of energy balance and body composition developed from similar work in mice. This model links PF-05231023 administration and washout to changes in food intake, which in turn drives changes in body weight. The model is calibrated to and compared with recently published data from cynomolgus macaques treated with PF-05231023, demonstrating its accuracy in describing pharmacotherapy-induced weight loss in these animals. The results are consistent with the hypothesis that PF-05231023 decreases body weight in cynomolgus macaques solely by a reduction in food intake, with no direct effect on energy expenditure.
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spelling pubmed-49548432016-07-29 PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates Thompson, W. Clayton Zhou, Yingjiang Talukdar, Saswata Musante, Cynthia J. J Pharmacokinet Pharmacodyn Original Paper PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mechanisms of action remain unclear. In particular, there have been conflicting reports on the degree to which FGF21-induced weight loss in non-human primates is attributable to a decrease in food intake versus an increase in energy expenditure. Here, we present a semi-mechanistic mathematical model of energy balance and body composition developed from similar work in mice. This model links PF-05231023 administration and washout to changes in food intake, which in turn drives changes in body weight. The model is calibrated to and compared with recently published data from cynomolgus macaques treated with PF-05231023, demonstrating its accuracy in describing pharmacotherapy-induced weight loss in these animals. The results are consistent with the hypothesis that PF-05231023 decreases body weight in cynomolgus macaques solely by a reduction in food intake, with no direct effect on energy expenditure. Springer US 2016-07-12 2016 /pmc/articles/PMC4954843/ /pubmed/27405817 http://dx.doi.org/10.1007/s10928-016-9481-1 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Paper
Thompson, W. Clayton
Zhou, Yingjiang
Talukdar, Saswata
Musante, Cynthia J.
PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates
title PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates
title_full PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates
title_fullStr PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates
title_full_unstemmed PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates
title_short PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates
title_sort pf-05231023, a long-acting fgf21 analogue, decreases body weight by reduction of food intake in non-human primates
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4954843/
https://www.ncbi.nlm.nih.gov/pubmed/27405817
http://dx.doi.org/10.1007/s10928-016-9481-1
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