Graisse | EPFL Graph Search

La graisse est un corps gras se présentant à l’état solide à température ordinaire. Le terme s’oppose aux huiles qui se présentent sous forme liquide. On distingue les graisses des cires, de composition similaire mais qui possèdent un point de fusion supérieur à . La saponification, la fabrication du savon, se fait souvent à partir de graisses. Propriétés Propriétés physico-chimiques

Hydrophobie : la graisse, comme tous les corps gras, n'est pas hydrosoluble et ne se mélange pas avec l'eau (propriété appelée hydrophobie). C'est sur ce phénomène graissier de répulsion que le procédé d'imprimerie « offset » conventionnel est fondé, en créant une émulsion entre la solution de mouillage et l'encre grasse. Certaines substances partageant la propriété d'hydrophobie avec la graisse sont solubles dans cette dernière. Tel est le cas de certaines vitamines, de certains pesticides, de certains parfums de fleur, de certains métaux lourds et du tétrahydrocannabinol (THC),

Gene regulatory dynamics underlying brown fat cell differentiation

Rachana Narendra Pradhan

Adipose tissue is increasingly recognized as a dynamic, endocrine organ responsible for regulating metabolic homeostasis via the collective action of its two principal subtypes: white adipose tissue (WAT) and brown adipose tissue (BAT). Recently, the discovery of metabolically active brown fat reserves and brown in white fat (also known as "brite" or "beige" fat) in adult humans has prompted fundamental research to understand the development and function of brown adipocytes. The functional property of brown adipocytes is executed by the mitochondrial protein, Un- coupling Protein 1 (UCP1). UCP1 is responsible for uncoupling oxidative phosphorylation from ATP production thereby dissipating heat. The gene expression of Ucp1 is orchestrated by a multitude of transcriptional regulators and co-regulators that are distinct from those governing white adipocyte differentiation and function. However, in contrast to its counter- part, the white adipocyte, the gene regulatory mechanisms and transcriptional drivers of the brown adipocyte differentiation program remain elusive. Thus the focus of this thesis is to elucidate the gene regulatory network underlying brown fat cell differentiation and to decou- ple differentiation from the thermogenesis program using an integrative genomics approach. The main contributions of this work are as follows (1) construction of a comprehensive map integrating signaling, transcriptional and metabolic modules necessary for the activation of a brown adipocyte, (2) systematic, comprehensive analysis of transcriptional and chromatin state dynamics during brown fat cell differentiation leading to the identification of novel transcriptional regulators, (3) genomic characterization of the TF BCL6 during brown fat cell differentiation and (4) phenotypic characterization of a novel conditional BCL6 knockout mouse model.

EPFL2017

Reduced ech-6 expression attenuates fat-induced lifespan shortening in C. elegans

Wen Gao, Richardus Houtkooper, Yan Liu

Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan in Caenorhabditis elegans, while a basal expression of ech-6 was important for survival under normal dietary conditions. Lipidomics revealed that supplementation of fat in ech-6-silenced worms had marginal effects on lipid profiles, suggesting an alternative fat utilization for energy production. Transcriptomics further suggest a causal relation between the lysosomal pathway, energy production, and the longevity effect conferred by the interaction between ech-6 and fat diets. Indeed, enhancing energy production from endogenous fat by overexpressing lysosomal lipase lipl-4 recapitulated the lifespan effects of fat diets on ech-6-silenced worms. Collectively, these results suggest that the gene ech-6 is potential modulator of metabolic flexibility and may be a target for promoting metabolic health and longevity.

NATURE PORTFOLIO2022

From food to physiology characterization and in vitro digestion of milk products and investigation of postprandial metabolism and inflammation after a high-fat meal intake in a human nutrition intervention study

Flurina Schwander

According to the World Health Organization worldwide obesity has more than doubled since 1980. The World health statistics 2012 report shows that one in six adults is obese, one in ten diabetic and one in three has a raised blood pressure. Overweight and obesity are major risk factors for cardiovascular diseases,According to the World Health Organization worldwide obesity has more than doubled since 1980. The World health statistics 2012 report shows that one in six adults is obese, one in ten diabetic and one in three has a raised blood pressure. Overweight and obesity are major risk factors for cardiovascular diseases, diabetes and some cancers. The causes of overweight and obesity are mainly a decrease in physical activity and an increased intake of energy-dense foods leading to a positive energy balance. Not only dietary patterns play a major role in the development of obesity. Food composition also directly impacts on postprandial metabolism and inflammation and, in long term, may contribute to systemic low-grade inflammation, a characteristic associated with the obese state. Thus it is not surprising that there is a growing interest in better understanding the effect of different foods and food compounds on human metabolism and health. The aim of the NutriChip project is to develop a microfluidic chip device to screen foods and their compounds for health promoting, e.g. immune-modulatory, properties. Milk products have been chosen as a food model because their consumption has been shown to be associated with decreased levels of inflammatory markers (1), and also because technological and microbiological transformations allow the realization of various products, such as yoghurt and cheese, having potentially different physiological effects. This thesis covers the biochemical (products characterization and in vitro digestion) and physiological (human nutrition study) aspects of the NutriChip project. Initially, differently heat-treated and fermented milk products were characterized by a proteomic approach. Various fractionation methods were used for selectively enriching minor milk and bacterial proteins in different dairy products. Proteins were separated and identified by two dimensional (2D) gel-electrophoresis and liquid chromatography coupled to mass spectrometry (LC-MS/MS) analysis. All data are collected in an interactive platform, called protein atlas, which is now publicly available on http://www.foodle.ch/de/proteinstart. Currently, the database contains more than 200 different milk proteins and about 250 bacterial proteins. For a better in depth characterization of fermented products, a method for the enrichment of living bacterial cells has been developed. This method allows the investigation of bacterial proteomes under different fermentation conditions. The method was used to monitor the adaption of the yoghurt bacteria Lactobacillus bulgaricus and Streptococcus thermophilus during milk fermentation. Some well-known stress response proteins (chaperone proteins GroEL and DnaK) and various enzymes involved in the glycolysis pathway have been identified as a proof of concept. Another experiment aimed to investigate the bacterial proteome during cheese production with special regards towards the identification of enzymes involved in the formation of the cheese flavor compound 3-methylbutanal. An aminotransferase that catalyzes the first step in the conversion pathway from the amino acid leucine to the flavor compound 3-methylbutanal could be identified. A prerequisite for screening foods for health-modulating activity was the development of a static, three-step in vitro digestion model. The aim was to keep the model as physiological as possible and ideally perform the digestion on a small scale (volume < 15 mL). The digestion model has been thoroughly validated using pasteurized whole milk. The degradation of fat, carbohydrates and proteins into their basic constituents was consistent with human physiological values found in the literature. The system has been used to digest various milk products. With the two proteins α-s1-casein and β-lactoglobulin, a representative of the caseins and whey proteins, respectively, the influence of the fat content, heat treatment and fermentation of the products on their digestibility has been monitored. Particularly we also looked at the generation of bioactive peptides during the digestion process. Towards this aim, the identified peptides in the digestion experiments were compared with bioactive peptide sequences from the literature using the statistic program R. Over 50 milk protein-derived peptides containing bioactive peptide sequences, with e.g. antihypertensive, immune- and cyto-modulatory, opioid functions, could be identified. The next step in simulating the human digestive system is the intestinal transport. Therefore, a cell culture model mimicking the last step of digestion and final absorption of the nutrients, both steps being mediated by intestinal enterocytes, was established. For this aim, Caco-2 cells were used in a Transwell system with an upper and lower compartment containing cell culture medium. Digested milk products were added on top of the Caco-2 cell monolayer and medium was collected from the basolateral chamber for identification of transported, potential bioactive peptides. The final validation of the in vitro models needs the comparison with a human nutrition intervention study. We designed and conducted a dose-response intervention study to determine the caloric dose (500 kcal, 1’000 kcal, 1’500 kcal) of a high-fat meal needed to induce a postprandial metabolic and inflammatory response in normal weight and obese subjects. In our study, we investigated postprandial metabolism and inflammation by measuring classical clinical parameters such as glucose, insulin and triglycerides, as well as the inflammation markers C-reactive protein (CRP), interleukine-6 (IL-6) and endotoxin before and at various time points after the test meals consumption. Our study provided valuable clinical, mechanistic, and methodological insights into the metabolic response of subjects, varying in their metabolic health status, to increasing doses of a high-fat meal. This represents the basis for future studies aiming to investigate health-promoting properties of foods in general, as also their capability in lowering postprandial inflammation, a normal response mechanism after food ingestion. v diabetes and some cancers. The causes of overweight and obesity are mainly a decrease in physical activity and an increased intake of energy-dense foods leading to a positive energy balance. Not only dietary patterns play a major role in the development of obesity. Food composition also directly impacts on postprandial metabolism and inflammation and, in long term, may contribute to systemic low-grade inflammation, a characteristic associated with the obese state. Thus it is not surprising that there is a growing interest in better understanding the effect of different foods and food compounds on human metabolism and health. The aim of the NutriChip project is to develop a microfluidic chip device to screen foods and their compounds for health promoting, e.g. immune-modulatory, properties. Milk products have been chosen as a food model because their consumption has been shown to be associated with decreased levels of inflammatory markers (1), and also because technological and microbiological transformations allow the realization of various products, such as yoghurt and cheese, having potentially different physiological effects. This thesis covers the biochemical (products characterization and in vitro digestion) and physiological (human nutrition study) aspects of the NutriChip project. Initially, differently heat-treated and fermented milk products were characterized by a proteomic approach. Various fractionation methods were used for selectively enriching minor milk and bacterial proteins in different dairy products. Proteins were separated and identified by two dimensional (2D) gel-electrophoresis and liquid chromatography coupled to mass spectrometry (LC-MS/MS) analysis. All data are collected in an interactive platform, called protein atlas, which is now publicly available on http://www.foodle.ch/de/proteinstart. Currently, the database contains more than 200 different milk proteins and about 250 bacterial proteins. For a better in depth characterization of fermented products, a method for the enrichment of living bacterial cells has been developed. This method allows the investigation of bacterial proteomes under different fermentation conditions. The method was used to monitor the adaption of the yoghurt bacteria Lactobacillus bulgaricus and Streptococcus thermophilus during milk fermentation. Some well- known stress response proteins (chaperone proteins GroEL and DnaK) and various enzymes involved in the glycolysis pathway have been identified as a proof of concept. Another experiment aimed to investigate the bacterial proteome during cheese production with special regards towards the identification of enzymes involved in the formation of the cheese flavor compound 3-methylbutanal. An aminotransferase that catalyzes the first step in the conversion pathway from the amino acid leucine to the flavor compound 3-methylbutanal could be identified. v A prerequisite for screening foods for health-modulating activity was the development of a static, three-step in vitro digestion model. The aim was to keep the model as physiological as possible and ideally perform the digestion on a small scale (volume < 15 mL). The digestion model has been thoroughly validated using pasteurized whole milk. The degradation of fat, carbohydrates and proteins into their basic constituents was consistent with human physiological values found in the literature. The system has been used to digest various milk products. With the two proteins α-s1-casein and β-lactoglobulin, a representative of the caseins and whey proteins, respectively, the influence of the fat content, heat treatment and fermentation of the products on their digestibility has been monitored. Particularly we also looked at the generation of bioactive peptides during the digestion process. Towards this aim, the identified peptides in the digestion experiments were compared with bioactive peptide sequences from the literature using the statistic program R. Over 50 milk protein-derived peptides containing bioactive peptide sequences, with e.g. antihypertensive, immune- and cyto-modulatory, opioid functions, could be identified. The next step in simulating the human digestive system is the intestinal transport. Therefore, a cell culture model mimicking the last step of digestion and final absorption of the nutrients, both steps being mediated by intestinal enterocytes, was established. For this aim, Caco-2 cells were used in a Transwell system with an upper and lower compartment containing cell culture medium. Digested milk products were added on top of the Caco-2 cell monolayer and medium was collected from the basolateral chamber for identification of transported, potential bioactive peptides. The final validation of the in vitro models needs the comparison with a human nutrition intervention study. We designed and conducted a dose-response intervention study to determine the caloric dose (500 kcal, 1’000 kcal, 1’500 kcal) of a high-fat meal needed to induce a postprandial metabolic and inflammatory response in normal weight and obese subjects. In our study, we investigated postprandial metabolism and inflammation by measuring classical clinical parameters such as glucose, insulin and triglycerides, as well as the inflammation markers C-reactive protein (CRP), interleukine-6 (IL-6) and endotoxin before and at various time points after the test meals consumption. Our study provided valuable clinical, mechanistic, and methodological insights into the metabolic response of subjects, varying in their metabolic health status, to increasing doses of a high-fat meal. This represents the basis for future studies aiming to investigate health- promoting properties of foods in general, as also their capability in lowering postprandial inflammation, a normal response mechanism after food ingestion.

EPFL2013

Flurina Schwander

EPFL2013