Cargando…

Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice

Although dipeptidyl peptidase 4 (DPP4) is an adipokine known to positively correlate with adiposity, the effects of pharmacological DPP4 inhibition on body composition have not been fully understood. This study was aimed to assess the effects of DPP4 inhibitors on adiposity for the first time in the...

Descripción completa

Detalles Bibliográficos
Autores principales: Chae, Yu-Na, Kim, Tae-Hyoung, Kim, Mi-Kyung, Shin, Chang-Yell, Jung, Il-Hoon, Sohn, Yong Sung, Son, Moon-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669177/
https://www.ncbi.nlm.nih.gov/pubmed/26633898
http://dx.doi.org/10.1371/journal.pone.0144064
_version_ 1782404077388300288
author Chae, Yu-Na
Kim, Tae-Hyoung
Kim, Mi-Kyung
Shin, Chang-Yell
Jung, Il-Hoon
Sohn, Yong Sung
Son, Moon-Ho
author_facet Chae, Yu-Na
Kim, Tae-Hyoung
Kim, Mi-Kyung
Shin, Chang-Yell
Jung, Il-Hoon
Sohn, Yong Sung
Son, Moon-Ho
author_sort Chae, Yu-Na
collection PubMed
description Although dipeptidyl peptidase 4 (DPP4) is an adipokine known to positively correlate with adiposity, the effects of pharmacological DPP4 inhibition on body composition have not been fully understood. This study was aimed to assess the effects of DPP4 inhibitors on adiposity for the first time in the established obese mice model. The weight loss effects of multiple DPP4 inhibitors were compared after a 4 week treatment in diet-induced obese mice. In addition, a 2 week study was performed to explore and compare the acute effects of evogliptin, a novel DPP4 inhibitor, and exenatide, a glucagon-like peptide-1 (GLP-1) analogue, on whole body composition, energy consumption, various plasma adipokines and gene expression in white adipose tissue (WAT). After the 4 week treatment, weight loss and blood glucose reductions were consistently observed with multiple DPP4 inhibitors. Moreover, after 2-week treatment, evogliptin dose-dependently reduced whole body fat mass while increasing the proportion of smaller adipocytes. However, insulin sensitivity or plasma lipid levels were not significantly altered. In addition to increased active GLP-1 levels by plasma DPP4 inhibition, evogliptin also enhanced basal metabolic rate without reduction in caloric intake, in contrast to exenatide; this finding suggested evogliptin's effects may be mediated by pathways other than via GLP-1. Evogliptin treatment also differentially increased Ppargc1a expression, a key metabolic regulator, in WAT, but not in skeletal muscle and brown adipose tissue. The increased expression of the downstream mitochondrial gene, Cox4i1, was also suggestive of the potential metabolic alteration in WAT by DPP4 inhibitors. We are the first to demonstrate that pharmacological DPP4 inhibition by evogliptin directly causes fat loss in established obese mice. In contradistinction to exenatide, the fat-loss effect of DPP4 inhibitor is partly attributed to enhanced energy expenditure along with metabolic changes in WAT. These results provide insight into the regulation of energy storage in WAT caused by DPP4 inhibition.
format Online
Article
Text
id pubmed-4669177
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-46691772015-12-10 Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice Chae, Yu-Na Kim, Tae-Hyoung Kim, Mi-Kyung Shin, Chang-Yell Jung, Il-Hoon Sohn, Yong Sung Son, Moon-Ho PLoS One Research Article Although dipeptidyl peptidase 4 (DPP4) is an adipokine known to positively correlate with adiposity, the effects of pharmacological DPP4 inhibition on body composition have not been fully understood. This study was aimed to assess the effects of DPP4 inhibitors on adiposity for the first time in the established obese mice model. The weight loss effects of multiple DPP4 inhibitors were compared after a 4 week treatment in diet-induced obese mice. In addition, a 2 week study was performed to explore and compare the acute effects of evogliptin, a novel DPP4 inhibitor, and exenatide, a glucagon-like peptide-1 (GLP-1) analogue, on whole body composition, energy consumption, various plasma adipokines and gene expression in white adipose tissue (WAT). After the 4 week treatment, weight loss and blood glucose reductions were consistently observed with multiple DPP4 inhibitors. Moreover, after 2-week treatment, evogliptin dose-dependently reduced whole body fat mass while increasing the proportion of smaller adipocytes. However, insulin sensitivity or plasma lipid levels were not significantly altered. In addition to increased active GLP-1 levels by plasma DPP4 inhibition, evogliptin also enhanced basal metabolic rate without reduction in caloric intake, in contrast to exenatide; this finding suggested evogliptin's effects may be mediated by pathways other than via GLP-1. Evogliptin treatment also differentially increased Ppargc1a expression, a key metabolic regulator, in WAT, but not in skeletal muscle and brown adipose tissue. The increased expression of the downstream mitochondrial gene, Cox4i1, was also suggestive of the potential metabolic alteration in WAT by DPP4 inhibitors. We are the first to demonstrate that pharmacological DPP4 inhibition by evogliptin directly causes fat loss in established obese mice. In contradistinction to exenatide, the fat-loss effect of DPP4 inhibitor is partly attributed to enhanced energy expenditure along with metabolic changes in WAT. These results provide insight into the regulation of energy storage in WAT caused by DPP4 inhibition. Public Library of Science 2015-12-03 /pmc/articles/PMC4669177/ /pubmed/26633898 http://dx.doi.org/10.1371/journal.pone.0144064 Text en © 2015 Chae et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chae, Yu-Na
Kim, Tae-Hyoung
Kim, Mi-Kyung
Shin, Chang-Yell
Jung, Il-Hoon
Sohn, Yong Sung
Son, Moon-Ho
Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice
title Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice
title_full Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice
title_fullStr Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice
title_full_unstemmed Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice
title_short Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice
title_sort beneficial effects of evogliptin, a novel dipeptidyl peptidase 4 inhibitor, on adiposity with increased ppargc1a in white adipose tissue in obese mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669177/
https://www.ncbi.nlm.nih.gov/pubmed/26633898
http://dx.doi.org/10.1371/journal.pone.0144064
work_keys_str_mv AT chaeyuna beneficialeffectsofevogliptinanoveldipeptidylpeptidase4inhibitoronadipositywithincreasedppargc1ainwhiteadiposetissueinobesemice
AT kimtaehyoung beneficialeffectsofevogliptinanoveldipeptidylpeptidase4inhibitoronadipositywithincreasedppargc1ainwhiteadiposetissueinobesemice
AT kimmikyung beneficialeffectsofevogliptinanoveldipeptidylpeptidase4inhibitoronadipositywithincreasedppargc1ainwhiteadiposetissueinobesemice
AT shinchangyell beneficialeffectsofevogliptinanoveldipeptidylpeptidase4inhibitoronadipositywithincreasedppargc1ainwhiteadiposetissueinobesemice
AT jungilhoon beneficialeffectsofevogliptinanoveldipeptidylpeptidase4inhibitoronadipositywithincreasedppargc1ainwhiteadiposetissueinobesemice
AT sohnyongsung beneficialeffectsofevogliptinanoveldipeptidylpeptidase4inhibitoronadipositywithincreasedppargc1ainwhiteadiposetissueinobesemice
AT sonmoonho beneficialeffectsofevogliptinanoveldipeptidylpeptidase4inhibitoronadipositywithincreasedppargc1ainwhiteadiposetissueinobesemice