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Program
Nutriomics : a little bit of history
Nutriomics team project aims at understanding the biological mechanisms involved in the development of human obesity and its comorbidities, its chronic maintenance and the resistance to weight loss. Our team was built after an Inserm 'Avenir' contract with the opportunity of forming a group made up of Inserm researchers, faculty researchers and bioinformatic experts, thus uniting complementary skills. Our mix INSERM/ University team, created by Inserm on 2006 January 1st (scientifically quoted A+ par AERES the French Agency of Research Evaluation), is based on a single theme, to be called Nutrition and Obesity: genetic and transcriptomic approaches (nutriomics). We joined the Cordelier Research Center (CRC) U872 in 2008. Our work led to original publications and hypothesis which are deeply explored notably in interaction with several teams of the CRC and national and international collaborators. Our activity is tidily linked to the heart and metabolism division at Pitié-Salpêtrière hospital, Paris at the novel Institute of Cardiometabolism and Nutrition (ICAN).Our working hypothesis is that obesity is a disease of adaptation to changes in modern life styles. If genetic determinants favor obesity development in response to multiple environmental modifications, molecular and structural adaptations of adipose tissue contribute to disease maintenance, the resistance to treatments and co morbidity development. By searching in the complexity of data from functional genomic studies and bioclinical phenotype characterization, we will be seeking to identify new physiopathological targets, biomarkers and predictors of disease stage of progression. A crux of the program is therefore the integration of data from a multiplicity of sources. Now we are elaborating our new project for the new 2014-2018 period.
Toward a new research programs
There will be 4 main research orientations derived from our previous pangenomic studies of human adipose tissue in lean and obese subjects before and after nutritional manipulation or bariatric surgery. Our approach relies on bioinformatic methods and has allowed us to show the mobilization of functional classes involving genes related to inflammation and adipose tissue remodeling, We identified candidate genes in the adipose tissue such as the serum amyloid A or the cathepsins, playing a possible role in linking the adipose tissue to the metabolic and cardiovascular complications of obesity. Beside the bioclinical resources we constituted, we develop methodological approaches to consider the multi-factorial aspects of obesity by integrating various sources of information resulting from genetics, clinical, functional genomic studies (DNA microarrays in particular), lipidomics and metabolomics.Research orientations
Task 1. Adipose tissue remodeling: inflammation/ immunity and fibrosisTask 2. Linking pathological alteration of adipose tissue with obesity comorbidities (focus on diabetes, liver and cardiometabolic diseases)
Task 3. Modulating adipose tissue alterations: impact of gut microbiota
Task 4. Data analysis and integration : Our bioinformatic research produced algorithms and tools whose applicability exceeds the particular framework of the multidimensional analysis of obesity. These contributions are the result of a permanent interaction between both the bioinformaticians and the biologists in our team.
Bariatric surgery : a study model
Obesity is characterized by the accumulation of excess body fat to an extent that health is adversely affected via the development of co-morbidities. Due to a scarcity of validated and safe therapies, Roux-en-Y gastric bypass (RYGB) has become an increasingly effective treatment for severely obese patients and is a remarkable model for improvement of metabolism and diabetes. Following this procedure, patients experience a significant loss of weight; however, an unexpected and major outcome with gastric bypass surgery was that deaths related to coronary heart disease and diabetes were reduced by more than 50% and 90%, respectively. Furthermore RYGB results in significant metabolic changes that lead to major improvements in blood glucose and insulin levels, insulin sensitivity and hormonal responses, as well as decreasing inflammatory markers.. Lipid metabolism is also modified following the procedure, as demonstrated by decreases in total cholesterol and LDL-cholesterol, and increases in HDL-cholesterol. . Significant changes in the secretion of gastric and intestinal peptides such as glucagon-like peptide-1 (GLP-1), ghrelin, and peptide YY have also been demonstrated following RYGB ]. While a growing body of evidence supports the overall health benefits of bariatric surgery to treat morbid obesity, such a procedure is also associated with risks including mortality (<1%) and several complications such as venous thromboembolism, gallstone formation, and nutritional deficiencies . Changes in body composition with weight loss include a decrease in fat free mass (about 25% of weight loss) that may be detrimental for metabolic capacities, mobility and nutritional status. Taken together, this procedure has a significant impact on a patient's whole-body metabolism and is therefore a unique model to understand the physiological and molecular mechanisms underlying the observed metabolic alterations. Bariatric surgery is a model of choice for many of our studies the last 10 years.Previous Programs (Clinical Research contract)
PHRC 2002-2007: Adiposity signals and obesity. Primary Investigator Prof. K ClémentCRC 2006-2008: Inflammation and Obesity. Primary Investigator Dr C Poitou-Bernert