Título:	GQ-16, a TZD-derived partial PPARγ agonist, induces the expression of thermogenesis- related genes in brown fat and visceral white fat and decreases visceral adiposity in obese and hyperglycemic mice
Autor(es):	Coelho, Michella S. Lima, Caroline Lourenço de Royer, Carine Silva, Janaina Barbosa da Oliveira, Fernanda C. B. Christ, Camila G. Pereira, Sidney Alcântara Báo, Sônia Nair Lima, Maria do Carmo Alves de Pitta, Marina Galdino da Rocha Pitta, Ivan da Rocha Neves, Francisco de Assis Rocha Amato, Angélica Amorim
Assunto:	Células Tecido adiposo Obesidade
Data de publicação:	3-Mai-2016
Editora:	Plos One
Referência:	COELHO, Michella S. et al. GQ-16, a TZD-derived partial PPARγ agonist, induces the expression of thermogenesis- related genes in brown fat and visceral white fat and decreases visceral adiposity in obese and hyperglycemic mice. Plos One, v. 11, n. 5, Article e0154310, 3 mai. 2016. Disponível em: <http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154310>. Acesso em: 14 jun. 2017. doi: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154310.
Abstract:	Background Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARγ activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARγ agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice. Methods Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPARγ agonist GQ-16 (40 mg/ kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content. Results GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis- related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT. Conclusion This study suggests for the first time that a partial PPARγ agonist may increase BAT activity and induce the expression of thermogenesis-related genes in visceral WAT. General Significance These findings suggest that PPARγ activity might be modulated by partial agonists to induce WAT browning and treat obesity.
Unidade Acadêmica:	Faculdade de Medicina (FMD)
Licença:	Copyright: © 2016 Coelho et al. 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 credited.
DOI:	https://doi.org/10.1371/journal.pone.0154310
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