EPFL, Route cantonale, 1015 Lausanne, SV Building, Room SV1717.1.
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Registration are closed.
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Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
A Circadian View of Nutrition and Metabolism
Circadian clocks are positioned at the cross road between nutritional cues and metabolic control. Thus, studying metabolism from a temporal and spatial perspective provides a unique niche that is expected to unveil novel fundamental principles related to basic metabolism and their nutritional control. In recent years my lab employed different methodologies, from biochemical approaches that identify protein-metabolite interactions through measurements of metabolic outputs in intact cells and living animals to high-throughput proteomics and metabolomics, to examine temporal and spatial aspects of metabolism. During my talk, I will discuss several examples emerging from our work on different groups of metabolites (e.g., lipids, polyamines, NAD) and on cellular metabolic processes (e.g., mitochondrial function) that shed new light in respect to their temporal and spatial intracellular organization and their nutritional control by different dietary regimens.
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Nouvel Hopital Civil (NHC), Strasbourg, IGBMC, Illkirch-Graffenstaden, France
The lysosome: A dangerous insulin shredder in diabetes ?
The pancreatic β cell harbors a nutrient sensing machinery that is coupled to secretion of insulin. While mechanisms governing regulation of insulin secretion in response to nutrients have been widely investigated, little is known about how nutrients impact on other basic cellular processes such as insulin granule turnover, autophagy and cellular growth, deregulation of all of which have been demonstrated to be involved in β cell failure in type 2 diabetes (T2D). There is an emerging endeavor of many investigators to develop therapeutic strategies for T2D patients targeting the β cell that go beyond improving insulin secretion.
We have recently discovered that enhanced lysosomal degradation of insulin granules inhibits autophagy in β cells under nutrient-poor conditions. While the latter mechansim represents an important adaptive cellular response to fasting, we now have evidence that enhanced lysosomal activity and insulin degradation confers progressive insulin loss and suppression of autophagy in β cells in T2D. Our work thus links lysosomal dysfunction to β cell failure in diabetes opening new therapeutic avenues to be explored in the near future.
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Centre Médical Universitaire (CMU), Dept PHYME, Room D06.1547, Medical faculty, University of Geneva, 1211 Genève 4, Switzerland
Regulation of energy homeostasis in health and metabolic disease
Mammals have two types of fat: brown and white, with opposing functions. Main function of the brown fat is to burn lipids and sugars in order to produce heat, a function that can be induced by cold exposure or exercise. Promotion of increased brown fat development in humans and experimental animals leads to increased energy expenditure and lean and healthy phenotype without causing dysfunction in other tissues, suggesting the manipulation of the fat stores as an important therapeutic perspective.
The gastrointestinal tract is the body’s largest endocrine organ that releases a number of regulatory peptide hormones that influence many physiological processes. The intestinal microbiota co-develops with the host, and its composition is influenced by several physiological changes. We demonstrated that the gut microbiota remodeling is an important contributor of the brown fat induction during cold and a key factor that promotes energy uptake by increasing the intestinal absorptive area thus orchestrating the overall energy homeostasis during increased energy demand.
I will discuss our recent research that aims at increasing the white fat browning and at modulating the intestinal plasticity in regulating the overall energy homeostasis from the gut microbiota-related perspective.
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1Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham NC 27708
2Duke Cancer Institute, Duke University Medical School, Durham NC
3Duke Molecular Physiology Institute, Duke University Medical School, Durham NC
An integrated analysis of intermediary metabolism in health and cancer
This presentation will discuss efforts to understand glucose and amino acid metabolism. First I will discuss efforts using computational modeling and metabolomics to understand the structure and function of glucose metabolism in cells. I will focus on a phenotype known as the Warburg Effect. The Warburg Effect (WE) is characterized by the increased metabolism of glucose to lactate. It is a common feature of cancers and proliferative diseases but its functions and differences from normal oxidative metabolism are not completely understood. Next I will focus on a network known as one carbon metabolism that integrates nutritional status from multiple sources including glucose to generate multiple biological outputs including anabolic and redox metabolism. This network provides the substrates for methyl groups that mediate the epigenetic status of cells. I will provide evidence that variation in the basal activity of one carbon metabolism is necessary and sufficient to determine methylation status of key epigenetic marks on histones. This finding provides a link between nutrient status and chromatin biology.
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Metabolomics platform, Faculty of Biology and Medicine, UNIL | University of Lausanne, Lausanne, Switzerland
Metabolomics: Beyond Biomarkers and Toward Mechanism
Metabolomics represents the apogee of the omics trilogy in the systems biology puzzle, where metabolites serve as a readout of cellular activity directly associated with phenotype. Many challenges, from analytical to computational, are progressively being overcome and metabolomics is expanding its impact beyond biomarker discovery to provide unique insight into cellular molecular mechanisms. This presentation will focus on developments in metabolomic workflow to study tissue-specific metabolic response, and primarily brain metabolism to examine the metabolic traits of the healthy aging brain. The advancements in experimental design, bioinformatics tools, tissue metabolite imaging and stable isotope-assisted approach will be outlined and discussed in the context of brain metabolism research.