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https://hdl.handle.net/10316/104799
Título: | Chenodeoxycholic Acid Has Non-Thermogenic, Mitodynamic Anti-Obesity Effects in an In Vitro CRISPR/Cas9 Model of Bile Acid Receptor TGR5 Knockdown | Autor: | Teodoro, João S. Machado, Ivo F. Castela, Ana C. Amorim, João A. Jarak, Ivana Carvalho, Rui A. Palmeira, Carlos M. Rolo, Anabela P. |
Palavras-chave: | CDCA; TGR5; mitochondria; mitophagy; CRISPR/Cas9; 3T3-L1 | Data: | 29-Out-2021 | Editora: | MDPI | Projeto: | UIDB/04539/2020 UIDP/04539/2020 SFRH/BPD/94036/2013 CEECIND/4400/2017 HEALTHYAGING 2020 CENTRO-01-0145- FEDER-000012 FCT - PhD scholarship (PD/BD/114173/2016) |
Título da revista, periódico, livro ou evento: | International Journal of Molecular Sciences | Volume: | 22 | Número: | 21 | Resumo: | Bile acids (BA) have shown promising effects in animal models of obesity. However, the said effects are thought to rely on a thermogenic effect, which is questionably present in humans. A previous work has shown that the BA chenodeoxycholic acid (CDCA) can revert obesity and accelerate metabolism in animal and cell culture models. Thus, the aim of this study was to understand if this obesity reduction is indeed thermogenically-dependent. A CRISPR/Cas9 model of TGR5 (BA receptor) knockdown in 3T3-L1 adipocytes was developed to diminish thermogenic effects. Various parameters were assessed, including mitochondrial bioenergetics by Seahorse flux analysis, oxidative stress and membrane potential by fluorometry, intermediary metabolism by NMR, protein content assessment by Western Blot, gene expression by qPCR, and confocal microscopy evaluation of mitophagy. CDCA was still capable, for the most part, of reversing the harmful effects of cellular obesity, elevating mitophagy and leading to the reduction of harmed mitochondria within the cells, boosting mitochondrial activity, and thus energy consumption. In summary, CDCA has a non-thermogenic, obesity reducing capacity that hinges on a healthy mitochondrial population, explaining at least some of these effects and opening avenues of human treatment for metabolic diseases. | URI: | https://hdl.handle.net/10316/104799 | ISSN: | 1422-0067 | DOI: | 10.3390/ijms222111738 | Direitos: | openAccess |
Aparece nas coleções: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Chenodeoxycholic-acid-has-nonthermogenic-mitodynamic-antiobesity-effects-in-an-in-vitro-crisprcas9-model-of-bile-acid-receptor-tgr5-knockdownInternational-Journal-of-Molecular-Sciences.pdf | 2.06 MB | Adobe PDF | Ver/Abrir |
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