High-Fat Diet: Bacteria Interactions Promote Intestinal Inflammation Which Precedes and Correlates with Obesity and Insulin Resistance in Mouse (original) (raw)
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Metabolism, 2016
Background. The obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis and the gut microbiota. Methods. We fed C57BL6/J mice 3 different HFDs with decreasing protein:carbohydrate ratios for 8 weeks and compared the results to a LFD reference group. We analyzed the gut microbiota composition by 16S rDNA amplicon sequencing and the intestinal gene expression by real-time PCR. Whole body glucose homeostasis was evaluated by insulin and glucose tolerance tests as well as by a hyperinsulinemic euglycemic clamp experiment. Results. Compared with LFD-fed reference mice, HFD-fed mice, irrespective of protein:carbohydrate ratio, exhibited impaired glucose tolerance, whereas no differences were observed during insulin tolerance tests. The hyperinsulinemic euglycemic clamp revealed tissue-specific effects on glucose homeostasis in all HFD-fed groups. HFD-fed mice exhibited decreased insulin-stimulated glucose uptake in white but not in brown adipose tissue, and sustained endogenous glucose production under insulin-stimulated conditions. We observed no impairment of insulin-stimulated glucose uptake in skeletal muscles of different fiber type composition. HFD-feeding altered the gut microbiota composition
PLoS ONE, 2012
We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD). Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80⁺) was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P = 0.020) and serum levels of serum amyloid A3 (131%; P = 0.008) but reduced circulating adiponectin (64%; P = 0.011). In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P = 0.025) respectively and TNF-α mRNA level was 6.6-fold higher (P = 0.037). HFD reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P = 0.004) in fecal microbiota. Correlations were found between abundances of Lactobacillus (r = 0.52; P = 0.013) and Oscillibacter (r = -0.55; P = 0.007) with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P = 0.020), TNF-α (2.5-fold, P<0.001) and IL-6 mRNA levels (2.5-fold; P = 0.008) in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P = 0.006) but neither TNF-α nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity.
Evidence on the role of gut microbes in obesity Revisión
Obesity results from a positive energy im- balance and it is associated with a chronic low-grade inflammation. The microbiota that populates the gut is considered a novel factor that, together with lifestyle, may be involved in obesity. On the one hand, the gut microbiota is globally involved in energy metabolism by im- proving the host's ability to extract and store energy from the diet. On the other, the com- mensal microbiota regulates immune functions, protecting the host from infections and chronic inflammation. Saturated lipids and Gram- negative bacteria trigger similar proinflamma- tory responses through their recognition by the same receptors of innate immune cells and adipocytes, associated with obesity and insulin resistance. Metabolic endotoxaemia is also a possible inflammatory factor causative of insu- lin resistance development and weight gain in animal models. In contrast, the administration of certain prebiotics may reverse this process and restore the gut balan...
Interaction Between Obesity and the Gut Microbiota: Relevance in Nutrition
Annual Review of Nutrition, 2011
This review examines mechanisms by which the bacteria present in the gut interact with nutrients and host biology to affect the risk of obesity and associated disorders, including diabetes, inflammation, and liver diseases. The bacterial metabolism of nutrients in the gut is able to drive the release of bioactive compounds (including short-chain fatty acids or lipid metabolites), which interact with host cellular targets to control energy metabolism and immunity. Animal and human data demonstrate that phylogenic changes occur in the microbiota composition in obese versus lean individuals; they suggest that the count of specific bacteria is inversely related to fat mass development, diabetes, and/or the low levels of inflammation associated with obesity. The prebiotic and probiotic approaches are presented as interesting research tools to counteract the drop in target bacteria and thereby to estimate their relevance in the improvement of host metabolism. 3.1 Review in Advance first posted online on May 11, 2011. (Changes may still occur before final publication online and in print.) Changes may still occur before final publication online and in print
Review Article Obesity as a Consequence of Gut Bacteria and Diet Interactions
Obesity is a major public health concern, caused by a combination of increased consumption of energy-dense foods and reduced physical activity, with contributions from host genetics, environment, and adipose tissue inflammation. In recent years, the gut microbiome has also been found to be implicated and augmented research in mice and humans have attributed to it both the manifestation and/or exacerbation of this major epidemic and vice versa. At the experimental level, analysis of fecal samples revealed a potential link between obesity and alterations in the gut flora (drop in Bacteroidetes and increase in Firmicutes), the specific gut microbiome being associated with the obese phenotype. Conventionally raised mice were found to have over 40% more total body fat compared with those raised under germ-free conditions, while conventionalization of germ-free mice resulted in a significant increase in total body fat. Similarly, the sparse data in humans supports the fact that fat storage is favoured by the presence of the gut microbiota, through a multifaceted mechanism. Efforts to identify new therapeutic strategies to modulate gut microbiota would be of high priority for public health, and to date, probiotics and/or prebiotics seem to be the most effective tools.
Gut microbiota as a key player in triggering obesity, systemic inflammation and insulin resistance
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
Obesity-related systemic inflammation contributes to develop insulin resistance. The main factors involved in the relationship of obesity with systemic inflammation and insulin resistance have not been completely elucidated. Microbiota includes around 1013 to 1014 microbes harboring the human gut, which are clustered in approximately a thousand different bacterial species. Several studies suggest that imbalance in the intestinal bacterial population could result in obesity, systemic inflammation and metabolic dysfunction. Here, we review the main bacterial groups observed in obesity as well as their possible role in increasing the intestinal permeability and lipopolysaccharide-related endotoxemia. Furthermore, we point out the role of intestinal dysbiosis in the inflammatory activation of macrophages with the ability to infiltrate in the visceral adipose tissue and induce insulin resistance. Finally, we discuss the apparent beneficial use of prebiotics and probiotics in ameliorating...