[PMID]: | 29351550 |
[Au] Autor: | Rachid TL; Silva-Veiga FM; Graus-Nunes F; Bringhenti I; Mandarim-de-Lacerda CA; Souza-Mello V |
[Ad] Endereço: | Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. |
[Ti] Título: | Differential actions of PPAR-α and PPAR-ß/δ on beige adipocyte formation: A study in the subcutaneous white adipose tissue of obese male mice. |
[So] Source: | PLoS One;13(1):e0191365, 2018. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND AND AIMS: Obesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-ß/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice. MATERIAL AND METHODS: Sixty animals were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for ten weeks. Then each group was re-divided to begin the treatments that lasted 4 weeks, totalizing six groups: C, C-α (C plus PPAR-α agonist, 2.5 mg/kg BM), C-ß (C plus PPAR-ß/δ agonist, 1 mg/kg BM), HF, HF-α (HF plus PPAR-α agonist), HF-ß (HF plus PPAR-ß/δ agonist). RESULTS: HF animals presented with overweight, glucose intolerance and subcutaneous white adipocyte hypertrophy. Both treatments significantly attenuated these parameters. Browning, verified by UCP1 positive beige cells and enhanced body temperature, was just observed in PPAR-α treated groups. PPAR-α agonism also elicited an enhanced gene expression of the thermogenesis effector UCP1, the beige-selective gene TMEM26 and the PRDM16, an essential gene for brown-like phenotype maintenance in the beige adipocytes when compared to their counterparts. The enhanced CIDEA and the reduced UCP1 gene levels might justify the white phenotype predominance after the treatment with the PPAR-ß/δ agonist. CONCLUSIONS: This work provides evidence that the PPAR-ß/δ agonist ameliorated metabolic disorders through enhanced beta-oxidation and better tolerance to glucose, whereas the PPAR-α agonism was confirmed as a promising therapeutic target for treating metabolic diseases via beige cell induction and enhanced thermogenesis. |
[Mh] Termos MeSH primário: |
Adipócitos Bege/efeitos dos fármacos Obesidade/tratamento farmacológico PPAR alfa/agonistas PPAR delta/agonistas PPAR beta/agonistas
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[Mh] Termos MeSH secundário: |
Adipócitos Bege/metabolismo Adipócitos Bege/patologia Tecido Adiposo Branco/efeitos dos fármacos Tecido Adiposo Branco/metabolismo Tecido Adiposo Branco/patologia Adiposidade/efeitos dos fármacos Animais Glicemia/metabolismo Peso Corporal/efeitos dos fármacos Tamanho Celular/efeitos dos fármacos Dieta Hiperlipídica/efeitos adversos Ingestão de Energia/efeitos dos fármacos Expressão Gênica/efeitos dos fármacos Intolerância à Glucose/tratamento farmacológico Hiperinsulinismo/tratamento farmacológico Masculino Camundongos Camundongos Endogâmicos C57BL Obesidade/metabolismo Obesidade/patologia Termogênese/efeitos dos fármacos Proteína Desacopladora 1/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Blood Glucose); 0 (PPAR alpha); 0 (PPAR delta); 0 (PPAR-beta); 0 (Ucp1 protein, mouse); 0 (Uncoupling Protein 1) |
[Em] Mês de entrada: | 1803 |
[Cu] Atualização por classe: | 180305 |
[Lr] Data última revisão:
| 180305 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 180120 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0191365 |
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