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Nutriomics: Nutrition & Obesity – Systemic Approaches

Principal investigator :
Karine Clément, MD, Ph.D.

Research team :

Researchers and clinicians: Michèle Guerre-Millo, Sebastien André, Isabelle Dugail, Danièle Lacasa, Joan Tordjman, Christine Poitou, Judith Aron-Wisnewsky, Jean-Philippe Bastard, Nataliya Sokolovka, Jean-Daniel Zucker, Patrick Tounian, Béatrice Dubern, Fabrizio Andreelli
Engineers and technicians: Christine Rouault, Véronique Pelloux, Rohia Allili, Flavien Jacques, Sonia Mutel, Arnault Leclerc, Maria Pini
Administrative officer: Muriel Solignac
PhD students: Sophie Reggio, Heddi Souissi, Sothea Touch, Hélène Huvennes, Yueyun liu, Charles Caer
Post-docs: Aurélie Cotillard, Kavya Anjani, Carlota Dao, Eric Verger, Tuong Nguyen

[See all of Dr. Poitou’s videos here]
[See all of Prof. Clément’s videos here]

Progress has been made in understanding pathophysiological aspects of obesity progression and in the adipose tissue biology but significant gaps remain in understanding the pathological alterations of human adipose tissue in obesity and their links with related co-morbidities. New innovative modes of obesity treatments have to be identified. NutriOmic team objectives are thus to identify relevant pathophysiological targets and biomarkers associated with obesity progression and related complications. A main unifying working hypothesis is that inflammatory/immune unbalance in obesity, potentially influenced by modified (micro) environmental factors is central in adipose cell injuries. This has major consequences on the systemic homeostasis associated with the biological deterioration of tissues located in WAT vicinity or at distant sites. In this context, we propose that the gut microbiota has a profound impact on organ cross-talks. NutriOmic is developing programs to depict at cellular and tissue levels the cross talk between immune system and adipose cell phenotypes. The relationships between these perturbations and obesity comorbidities will be explored. NutriOmic also investigates the importance of environmental changes including nutritional switches on human metabolism and inflammation via modification of the gut microbiota. These aspects are addressed by 4 working themes; 1. Adipose remodeling and inflammation: deciphering cellular and molecular processes, 2. Fibrosis and inflammation in human adipose tissue: local and systemic consequences, 3. Improving cardiometabolic state and predicting responses to interventions: modulation of the gut microbiota is explored in this context by translational approaches, 4. Systems” biology and data integration. This last transversal theme uses bioinformatics approaches with multilevel data integration to ensure exploitation of research results towards the identification of signatures associated with obesity and comorbidity stages. The different research themes are closely interconnected and use in vitro and in vivo approaches as well as clinical studies and bioinformatic resources to better understand the complex nature of obesity pathophysiology and transfer in the future knowledge to innovative approaches in patient care.

FOCUS

The goal of NutriOmics is to explore the complex pathophysiology of obesity assessing organ cross-talks.


BIOSKETCH

Pr Karine Clément is full professor of Nutrition, Division of Cardiometabolism, Pitié-Salpêtrière hospital and at Paris 6 Pierre et Marie Curie university in Paris. From 2011 to 2016, she was the director of the Center of Excellence ICAN Institute de CardiometAbolism and Nutrition, dedicated to innovative Care, Research and training in the field of Cardiology and metabolic diseases. This institute aims at developing personalized medicine in the field of cardiometabolic diseases. KC’s team (Nutriomique) has been involved in genetic and functional genomics aspects of human obesity. Her work led to the identification of monogenic forms of obesity (Leptin receptor and MC4R mutations) and to several genetic risk factors in common obesity. She contributed to more than 200 international publications, reviews and many international conferences in the field. She performed a post-doctoral fellowship at Stanford University, CA, USA where she acquired competencies in gene profiling approaches applied to complex diseases (1999-2000). In 2001 she obtained a young INSERM “Avenir” team focused on the characterization of patterns of gene expression induced by environmental perturbations. Her group showed notably that inflammatory and remodeling genes in human adipose tissue are modulated by weight variation in parallel to macrophage infiltration changes. Deeper insight into mechanisms is now undertaken. In addition, the team is exploring the link between environment changes and functional modifications in the adipose tissue. The gut microbiota is of evidence a key actor of this link. She is a member and expert of several national and international scientific committees in obesity and metabolism and contributes to several European Networks in genetics and functional genomics (Diogenes, Hepadip, ADAPT, FLIP and coordinates METACARDIS www.metacardis.eu).


Publications

1. 1. Cotillard, A., Kennedy, S.P., Kong, L.C., Prifti, E., Pons, N., Le Chatelier, E., Almeida, M., Quinquis, B., Levenez, F., Galleron, N., Gougis, S., Rizkalla, S., Batto, J.-M., Renault, P., ANR MicroObes consortium, Doré, J., Zucker, J.-D., Clément, K., Ehrlich, S.D.., 2013. Dietary intervention impact on gut microbial gene richness. Nature 500, 585–588
2. Toubal A, Clément K, Fan R, Ancel P, Pelloux V, Rouault C, Veyrie N, Hartemann A, Treuter E, Venteclef N. Dysregulation of a GPS2/SMRT corepressor pathway in adipocytes coincides with adipose tissue inflammation in human obesity. J Clin. Invest, In press 2012
3. Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, Basdevant A, Guerre-Millo M, Poitou C, Zucker JD, Bedossa P, Clément K. Fibrosis in human adipose tissue: composition, distribution and link with lipid metabolism and fat mass loss. Diabetes. 2010 Nov;59(11):2817-25.
4. Furet JP*, Kong LC*, Tap J, Poitou C, Basdevant A, Bouillot JL, Mariat D, Corthier G, Doré J, Henegar C, Rizkalla S, Clément K. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010 Dec;59(12):3049-57
5. Liu J, Divoux A, Sun J, Zhang J, Clément K, Glickman JN, Sukhova GK, Wolters PJ, Du J, Gorgun CZ, Doria A, Libby P, Blumberg RS, Kahn BB, Hotamisligil GS, Shi GP. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med. 2009 Aug;15(8):940-5.

Nutrition & Obesity : Systemic Approach