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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-19022018-141931
Document
Author
Full name
Gabriela Virginia Moreira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Carvalho, Carla Roberta de Oliveira (President)
Curi, Rui
Gama, Patricia
Saad, Mario Jose Abdalla
Santos, Andrey dos
Title in Portuguese
Liraglutida promove mudança da microbiota intestinal com redução da massa adiposa e da esteatose hepática não-alcóolica em dois modelos animais de obesidade.
Keywords in Portuguese
Análogo GLP-1
EHNA
Liraglutida
Microbiota intestinal
Obesidade
Abstract in Portuguese
Analisamos a ação da liraglutida na flora intestinal e perda de peso de dois modelos de obesidade: por dieta hiperlipidica (HFD) e obesidade genética (ob/ob). Os modelos foram tratados com o fármaco durante duas semanas. Perfis metabólicos foram feitos por meio de testes glicêmicos e insulínicos, histologia do fígado, região cecal e coxins gordurosos, ingestão alimentar, peso corporal e metagenômica do conteúdo cecal. O tratamento induziu perda de peso com melhora dos níveis glicêmicos e redução da inflamação na região cecal e do fígado e foi capaz de reduzir o acúmulo de gordura hepática promovendo a redução da EHNA. A metagenômica mostrou mudança taxonômica geral, bem como a abundância relativa de bactérias envolvidas com peso e controle glicêmico:redução de Proteobacterias e aumento de Akkermansia muciniphila. Apresentamos evidências do fármaco revertendo DGHNA/EHNA e a perda de peso associados às mudanças da microbiota. Sugerimos uma lista de alvos bacterianos que podem interferir no metabolismo energético para o controle clinico de doenças metabólicas.
Title in English
Liraglutide changes gut microbiota and reduces hepatic steatosis and fat mass in two models of obesity mice.
Keywords in English
GLP-1 analogue
Gut microbiome
Liraglutide
NASH
Obesity
Abstract in English
The study analyzed the effects of liraglutide on gut microbiota and weight-loss in two obesity model: induced by high fat diet (HFD) and genetic obese mice (ob/ob). Models were treated with liraglutide for two weeks. Metabolic profiles were measured by glycemic and insulin test, histological liver, cecal region and fat pad morphologies, food intake, body weight and metagenomic of cecal contents. The treatment induced weight-loss, improvement of glycemic parameters and reduction of inflammatory cells in the cecum and the liver and reduced fat accumulation in liver reverting NASH. The metagenomic showed a general changed in taxonomic structure as well the relative abundance of weight-relevant:reduction of Proteobacteria and increases of Akkermansia muciniphila. We showed evidences that liraglutide leads to improvement of NASH and weight loss associated with changes in microbiota. Moreover, by the profile of the gut microbiota, we present a bacterial target list that may affect energetic metabolism inducing a metabolic clinical controlled profile.
 
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Release Date
2020-02-19
Publishing Date
2018-02-19
 
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