Ativação da via central anorexigênica pela Liraglutida (análogo do hormônio GLP-1) em modelo de obesidade induzida por dieta

• Ano de defesa: 2014
• Autor(a) principal: Vianna, André Rodrigues da Cunha Barreto
• Orientador(a): Mandarim-de-Lacerda, Carlos Alberto
• Banca de defesa: Gadelha, Mônica Roberto , Lacerda, Márcia Barbosa Águila Mandarim de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Biologia Humana e Experimental
• Departamento: Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes
• País: BR
• Palavras-chave em Português: Hipotálamo; Apetite; Dieta hiperlipídica; Termogênese; Obesidade
• Palavras-chave em Inglês: Hypothalamus; Appetite; High fat diet; Thermogenesis
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/7864

In the present study, we investigated the central mechanisms and brown adipose tissue (BAT) thermogenesis underlying body mass (BM) loss observed with the administration of liraglutide (a glucagon-like peptide-1 analog). Four groups of 10 male C57BL/6 mice were studied: a standard chow group treated with vehicle (SC) or liraglutide (SC/Lir) and a high-fat group treated with vehicle (HF) or liraglutide (HF/Lir). The data demonstrates that liraglutide increased the anorexigenic pro-opiomelanocortin neuropeptide in the hypothalamus and diminished both the central leptin resistance and the suppressor of cytokine signaling-3 mRNA expression. Liraglutide administration improved adiponectin plasma levels and decreased both glucose intolerance and insulin resistance. In addition, both the SC and HF groups consumed the same amount of food, whereas the SC/Lir group consumed 17.5% less food compared with the SC group, and the HF/Lir group consumed 22.5% less food compared with the HF group. The final BM was 8.5% lower in the SC/Lir group compared with the SC group, and the BM was 16% lower in the HF/Lir group compared with the HF group. Furthermore, liraglutide administration increased oxygen consumption, carbon dioxide production, and decreased the respiratory exchange ratio. In addition, liraglutide increased the beta-3 adrenergic receptor, mitochondrial uncoupling protein-1, guanosine-5'-triphosphate-binding protein and insulin-stimulated glucose transporter (GLUT)-4 in BAT. In conclusion, liraglutide administration in diet-obese mice activates the central anorexigenic pathway, diminishing the energy intake of these animals, acting synergistically with the increase in energy expenditure.