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

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. Impact statement 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.

Activation of the Wnt/ß-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice.

The Wnt/ß-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/ß-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active ß-catenin associated with significant increases in protein content and gene expression of ß-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor). Meanwhile, these alterations were not observed in pancreatic islets from 30 d HFD-fed mice, that do not display significant beta cell hyperplasia. These data suggest that the Wnt/ß-catenin pathway is activated in pancreatic islets during prediabetes and may play a role in the induction of the compensatory beta cell hyperplasia observed at early phase of T2DM.

Influence of gender and time diet exposure on endocrine pancreas remodeling in response to high fat diet-induced metabolic disturbances in mice.

In this study, we investigated a possible sexual dimorphism regarding metabolic response and structural and functional adaptations of the endocrine pancreas after exposure to a high-fat diet (HFd). On chow diet, male and female C57BL/6/JUnib mice showed similar metabolic and morphometric parameters, except that female islets displayed a relatively lower ß-cell:non-ß-cell ratio. After 30 days on HFd, both male and female mice showed increased weight gain, however only the males displayed glucose intolerance associated with high postprandial glycemia when compared to their controls. After 60 days on HFd, both genders became obese, hyperglycemic, hyperinsulinemic, insulin resistant and glucose intolerant, although the metabolic changes were more pronounced in males, while females displayed greater weight gain. In both genders, insulin resistance induced by HFd feeding was compensated by expansion of ß-cell mass without changes in islet cytoarchitecture. Interestingly, we found a strong correlation between the degree of ß-cell expansion and the levels of hyperglycemia in the fed state: male mice fed a 60d-HFd, showing higher glycemic levels also displayed a greater ß-cell mass increase in comparison with female mice. Additionally, sexual dimorphism was also observed regarding the source of ß-cell mass expansion following 60d-HFd: while in males, both hypertrophy and hyperplasia (revealed by morphometry and Ki67 immunoreaction) of ß-cells were observed, female islets displayed only a significant increase in ß-cell size. In conclusion, this study describes gender differences in metabolic response to high fat diet, paralleled by distinct compensatory morphometric changes in pancreatic islets.

Diferentes níveis de incorporação de farinha de resíduos de jundiás (Rhamdiaquelen) cultivados na dieta / Different levels of jundiá waste meal in the diet

O estudo foi desenvolvido no Laboratório de Piscicultura do Departamento de Zootecnia da Universidade Federal de Santa Maria, com duração de oito semanas, de abril a junho de 2011. O objetivo foi definir o melhor nível de incorporação do resíduo de peixes na alimentação de juvenis de jundiá, em sistema de recirculação d'água, utilizando-se 450 alevinos de jundiás, com peso médio inicial de 7,2±0,27g. Foram testadas cinco diferentes dietas, em três repetições, com níveis diferentes (0; 3,75; 7,5; 15; e 30 por cento) de incorporação de farinha de carcaça de jundiás com vísceras (FCJCV). As dietas continham, aproximadamente, 37 por cento de PB e 3200kcal de EM/kg de dieta. Foram coletados dados de ganho em peso diário, sobrevivência, fator de condição, taxa de crescimento específico, conversão alimentar aparente, rendimento de carcaça, taxa de eficiência proteica e deposição de proteína e lipídio corporal. O maior ganho de peso foi para o nível 30 por cento de inclusão de FCJCV, com peso final de 45,47g e ganho em peso diário de 0,68g/dia. A dieta com nível de 30% de inclusão de FCJCV apresentou melhores valores para taxa de crescimento específico (3,34 por cento/dia), conversão alimentar aparente (1,05: 1), biomassa final 1.105,45g, deposição proteica corporal (64,9mg/dia), taxa de eficiência proteica (1,9) e coeficiente de retenção proteica (1,96 por cento). Concluiu-se que a utilização de farinha de resíduos de processamento de jundiá no nível de 30% de inclusão na dieta foi a que apresentou maior eficiência no desenvolvimento de juvenis de jundiá...

The study was carried out at the Fish Farming Laboratory of the Animal Science Department, Federal University of Santa Maria, during 8 weeks, from April to June 2011. The objective of this study was to define the best level of incorporation of waste in food fish of juvenile Jundiá in water recirculation system using 450 fingerlings of jundiá with initial average weight of 7.2±0.27g. We tested 5 different diets in three repetitions with different levels of incorporation of carcasse jundiá with viscera meal (FCJCV) (0, 3.75, 7.5, 15, and 30 percent). The diets contained 37 percent CP and 3200kcal/kg of ME. Data were collected from daily weight gain, survival, condition factor, specific growth rate, feed conversion, carcass yield, protein efficiency ratio and deposition of body protein and lipid. The weight gain was greater with the inclusion of 30 percent FCJCV with final weight of 45.47g and daily weight gain of 0.68g/day. The diet with inclusion of 30 percent FCJCV showed better values for specific growth rate (3.34 percent/day), feed conversion ratio (1.05: 1), final biomass (1105.45g), body protein deposition (64.9mg/day), protein efficiency ratio (1.9) and protein retention coefficient (1.96 percent). In conclusion, the use of processing waste meal of jundiá in the level of 30 percent in the diet showed the highest efficiency in the development of juvenile jundiá...

Crescimento de juvenis de jundiá (Rhamdia quelen) com diferentes proporções de amilose: amilopectina na dieta / Growth of jundiá juveniles (Rhamdia quelen) with different proportions of amylose:amylopectin in diet

Crescimento e características de carcaça do jundiá (Rhamdia quelen) foram avaliados após 60 dias de alimentação com diferentes proporções de amilose:amilopectina na dieta. Foram criados 240 peixes (peso inicial de 34,3±4,3g) em sistema de recirculação de água constituído de 12 unidades experimentais de 280L. Foram testadas três dietas com as proporções amilose:amilopectina de: T417 = com 26 por cento de amilose, T416 = com 16 por cento de amilose e TMOCHI = com 0 por cento de amilose. Os peixes foram alimentados duas vezes por dia, às 8h e 30min e às 16 horas. A cada 15 dias, foram feitas biometrias para ajuste da quantidade de alimento ofertado. A proporção amilose:amilopectina no amido das dietas não influenciou o crescimento, os rendimentos de carcaça e a composição corporal dos peixes. Conclui-se que o jundiá tem potencial para utilizar fontes de amido compostas por até 26 por cento de amilose sem alterar a digestibilidade dos nutrientes e a deposição de gordura.

The growth and carcass traits of jundiá (Rhamdia quelen) after 60 days being fed with different amylose:amylopectin ratio in diet were evaluated. Two hundred and forty fish (initial weight of 34.3±4.3g) were raised in water re-use system with 12 units of 280L. Three diets were tested with amylose:amylopectin ratios: T417 = 26 percent amylose, T416 = 16 percent amylose and TMOCHI = 0 percent amylose. The fish were fed twice a day at 8:30 and 16:00h. Every 15 days the amount of food offered was ajusted. The amylose:amylopectin ratio in the starch of the diet did not affect growth, carcass and body composition of fish. This demonstrates that the jundiá has the potential to use starchy sources consisting of up to 26 percent amylose without altering the digestibility of nutrients and fat deposition.