Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice

Autor(es)

Matheus, V. A. ; Monteiro, L. C. S. ; Oliveira, R. B. ; Maschio, D. A. ; Collares-Buzato, C. B.

• Tipo de documento: Artigo Científico
• Fonte: Experimental Biology and Medicine; v. 242, n. 12, p. 1214-1226, JUN 2017.
• Citações Web of Science: 15

Resumo

In this study, we investigated the effect of diet supplementation with sodium butyrate (5% w/w), a short-chain fatty acid produced by the intestinal microbiota, on metabolic parameters, body adiposity, hepatic and pancreatic lipid accumulation, beta cell function/mass as well as on the structure and function of the tight junction-mediated intestinal epithelial barrier in both normal and obese/prediabetic C57 mice fed a regular (control) or high-fat diet for 60 days, respectively. Butyrate treatment significantly inhibited all the high-fat-induced metabolic dysfunctions evaluated, i.e. significantly reduced the weight gain and body adiposity as well as the insulin resistant state, hyperglycemia and hyperinsulinemia, without changing food intake. In addition, high-fat-fed mice treated with this short-chain fatty acid displayed no compensatory hyperplasia of pancreatic beta cells nor marked hepatic steatosis as seen in prediabetic mice after high-fat diet only. Isolated pancreatic islets from high-fat-fed mice treated with butyrate showed improvement of the insulin secretion, which was associated with a significant decrease in lipid accumulation within the pancreas. Butyrate enhanced the intestinal epithelial barrier, as revealed by the FITC-Dextran permeability assay, which was accompanied by a significant increase in the junctional content of the tight junction-associated claudin-1 in intestinal epithelia of jejunum, ileum, and colon of both control and high-fat mice. In conclusion, our results showed that diet supplementation with butyrate inhibits the deleterious effects of high-fat diet intake on metabolic parameters and structure/function of several tissues/organs associated with type 2 diabetes mellitus in a mouse model, suggesting a potential use of this short-chain fatty acid in the treatment of this endocrine-metabolic disorder. (AU)

• Processo FAPESP: 13/15676-0 - Modulação in vitro da barreira epitelial intestinal mediada pelas junções de oclusão (tight junctions): efeito da exposição a nutrientes (glicose e ácidos graxos), à insulina, e à microflora bacteriana de animais pré-diabéticos
• Beneficiário: Carla Beatriz Collares Buzato
• Modalidade de apoio: Auxílio à Pesquisa - Regular