Project description:To understand how dietary fiber affects microglial transcriptome at early stage, we fed mice diets releasing different amount of fiber and profiled microglia at 3 weeks. We found that fiber significantly altered the transcriptomic signature of microglia.
Project description:There is increased interest in the potential protective role of dietary Ca in the development of metabolic disorders related to the metabolic syndrome. Ca-induced intestinal precipitation of fatty acids and bile acids as well as systemic metabolic effects of Ca on adipose tissue is proposed to play a causal role. In this experiment, we have studied all these aspects to validate the suggested protective effect of Ca supplementation, independent of other dietary changes, on the development of diet-induced obesity and insulin resistance. In our diet intervention study, C57BL/6J mice were fed high-fat diets differing in Ca concentrations (50 v. 150 mmol/kg). Faecal excretion analyses showed an elevated precipitation of intestinal fatty acids (2·3-fold; P < 0·01) and bile acids (2-fold; P < 0·01) on the high-Ca diet. However, this only led to a slight reduction in fat absorption (from 98 to 95 %; P < 0·01), mainly in the distal small intestine as indicated by gene expression changes. We found no effect on body-weight gain. Lipolysis and lipogenesis-related parameters in adipose tissue also showed no significant changes on the high-Ca diet, indicating no systemic effects of dietary Ca on adiposity. Furthermore, early gene expression changes of intestinal signaling molecules predicted no protective effect of dietary Ca on the development of insulin resistance, which was confirmed by equal values for insulin sensitivity on both diets. Taken together, our data do not support the proposed protective effect of dietary Ca on the development of obesity and/or insulin resistance, despite a significant increase in fecal excretion of fatty acids and bile acids. Keywords: Diet intervention study Nine-week-old mice were fed a high fat purified diet with a low calcium concentration of 50mmol/kg (LCa diet) or a high calcium concentration of 150mmol/kg (HCa diet) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. For microarray analysis, after 2 weeks of diet intervention, 6 mice per diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on pooled mucosal scrapings.
Project description:Consumption of diets rich in fibers has been associated with several beneficial effects on gastrointestinal health. However, detailed studies on the molecular effects of fibers in colon are limited. In this study we investigated and compared the influence of five different fibers on the mucosal transcriptome, and luminal microbiota and SCFA concentrations in murine colon. Mice were fed diets enriched with fibers that differed in carbohydrate composition, namely inulin (IN), oligofructose (FOS), arabinoxylan (AX), guar gum (GG), resistant starch (RS) or a control diet (corn starch) for 10 days. Gene expression profiling revealed the regulation of specific, but also overlapping sets of epithelial genes by each fiber, which on a functional level were mainly linked to cell cycle and various metabolic pathways including fatty acid oxidation, tricarboxylic acid cycle, and electron transport chain. In addition, the transcription factor PPAR was predicted to be a prominent upstream regulator of these processes. Microbiota profiles were distinct per dietary fiber, but the fibers IN, FOS, AX and GG induced a common change in microbial groups. All dietary fibers, except resistant starch, increased SCFA concentrations but to a different extent. Multivariate data integration revealed strong correlations between the expression of genes involved in energy metabolism and the relative abundance of bacteria belonging to the group of Clostridium cluster XIVa, that are known butyrate producers. These findings illustrate the potential of multivariate data analysis to unravel simple relationships in complex systems. Keywords: Expression profiling by array Mice received a control diet, or a diet supplemented with 10% dietary fibers for 10 days. After an overnight fast colon was removed, epithelial cells were scraped off, and subjected to gene expression profiling.
Project description:Abstract: Our intake of ultra-processed foods has dramatically increased over the past few decades in line with the prevalence of obesity and diabetes, key risk factors for microvascular diseases such as chronic kidney disease (CKD). The extent to which long-term intake of highly processed food influences CKD outcome is unclear. Here, we show in rodent models that a highly processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glycation pathway, which generates Maillard reaction products within foods upon thermal processing, reversed kidney injury. Consequently, a highly processed diet leads to innate immune complement activation and local kidney inflammation via the potent proinflammatory effector molecule complement 5a (C5a). C5a receptor inhibition ameliorated albuminuria. In a mouse model of diabetes, a high resistant starch fiber diet led to a redistribution of the gut commensal consortium, prevented impaired gut barrier function and decreased the severity of kidney injury via suppression of complement. These results provide mechanistic insight into the role of highly processed foods on inflammation and chronic disease risk. One Sentence Summary: Ultra-processed diets promote chronic kidney disease
Project description:The aim of this study was to evaluate the responses of meat-type chicken to changes in dietary energy sources by comparing high-fiber high-fat vs. standard high-starch diets and using a transcriptomic approach in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells.
Project description:The aim of this study was to evaluate the responses of meat-type chicken to changes in dietary energy sources by comparing high-fiber high-fat vs. standard high-starch diets and using a transcriptomic approach in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells.
Project description:The aim of this study was to evaluate the responses of meat-type chicken to changes in dietary energy sources by comparing high-fiber high-fat vs. standard high-starch diets and using a transcriptomic approach in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells.
Project description:The aim of this study was to evaluate the responses of meat-type chicken to changes in dietary energy sources by comparing high-fiber high-fat vs. standard high-starch diets and using a transcriptomic approach in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells.
Project description:Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets led to hyperphagia, obesity and reduced lifespan. These effects were not due to elevated BCAA per se or hepatic mTOR activation, but rather the shift in balance between dietary BCAAs and other AAs, notably tryptophan and threonine. Increasing the ratio of BCAAs to these AAs resulted in hyperphagia and was linked to central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averted the health costs of a high BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes were not due to intrinsic toxicity; rather, to hyperphagia driven by AA imbalance.
Project description:This dataset contains proteomic data from mice with high or low weight gain in response to a high fat diet. Both host and microbial proteins are present. In the supplemental, there are also tables and supplementary files that can be used for replicating the bioinformatic analysis.
Abstract:
Consumption of refined high-fat, low-fiber diets promotes development of obesity and its associated consequences. While genetics play an important role in dictating susceptibility to such obesogenic diets, mice with nearly uniform genetics exhibit marked heterogeneity in their extent of obesity in response to such diets. This suggests non-genetic determinants play a role in diet-induced obesity. Hence, we sought to identify parameters that predict, and/or correlate with, development of obesity in response to an obesogenic diet. We assayed behavior, metabolic parameters, inflammatory markers/cytokines, microbiota composition, and the fecal metaproteome, in a cohort of mice (n=50) prior to, and the 8 weeks following, administration of an obesogenic high-fat low-fiber diet. Neither behavioral testing nor quantitation of inflammatory markers broadly predicted severity of diet-induced obesity. Although, the small subset of mice that exhibited basal elevations in serum IL-6 (n=5) were among the more obese mice in the cohort. While fecal microbiota composition changed markedly in response to the obesogenic diet, it lacked the ability to predict which mice were relative prone or resistant to obesity. In contrast, fecal metaproteome analysis revealed functional and taxonomic differences among the proteins associated with proneness to obesity. Targeted interrogation of microbiota composition data successfully validated the taxonomic differences seen in the metaproteome. While future work will be needed to determine the breadth of applicability of these associations to other cohorts of animals and humans, this study nonetheless highlights the potential power of gut microbial proteins to predict and perhaps impact development of obesity.