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

Abstract

Butyrate is a short-chain fatty acid produced by the intestinal microbiota through the fermentation of non-absorbable carbohydrates and proteins (e.g. fibers). Sodium butyrate incorporated into the diet displayed a protective action on metabolic, hepatic, pancreatic and intestinal alterations induced by high-fat diet in mice, resulting in significant inhibition of the development of a prediabetic state. Thus, our data suggest that butyrate may have a potential therapeutic use in the treatment of type 2 diabetes and related disorders. AbstractIn 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.

Butyrate protects against high‐fat diet‐induced atherosclerosis via up‐regulating ABCA1 expression in apolipoprotein E‐deficiency mice

“…Consumption of dietary fat promotes the development of hepatic steatosis, which is closely associated with obesity and carotid atherosclerosis (Bhatia et al, ; Mahfood Haddad, Hamdeh, Kanmanthareddy, & Alla, ). Butyrate administration significantly alleviated the HFD‐induced hepatic steatosis in ApoE −/− mice, as previously reported (Matheus, Monteiro, Oliveira, Maschio, & Collares‐Buzato, ; Mattace Raso et al, ). To find the differential expressed genes that may affect fatty liver and atherosclerosis, transcriptome profiling of mice liver was investigated.…”

Soluble Fiber and Insoluble Fiber Regulate Colonic Microbiota and Barrier Function in a Piglet Model

“…Significant positive correlations between colonic propionate concentrations and TFF expression were observed in rats [43]. Diet supplementation with butyrate inhibited the disruption of the intestinal epithelial barrier induced by high-fat diet via upregulating the gene expression of CLDN-1 [57]. In the present study, the highest concentration of SCFAs might be one of the reasons that SDF diet was more efficient in regulating colonic barrier function than other groups.…”

Breastmilk Lipids and Oligosaccharides Influence Branched Short‐Chain Fatty Acid Concentrations in Infants with Excessive Weight Gain

“…At 9 months of age, we observed a lower fecal butyrate concentration in the HW‐group, which may contribute to the EWG through multiple mechanisms. Dietary butyrate supplementation alleviates adipogenesis, reduces weight gain, decreases lipid accumulation in pancreas, and improves β‐cell insulin sensitivity in high‐fat diet fed mice.…”