Equipe 9

Team 9 : Jaap Neels
ADAPTIVE RESPONSES TO IMMUNO-METABOLIC DYSREGULATIONS

Research Projects
In most industrialized countries, obesity has become epidemic, resulting in a dramatic rise of associated pathologies (e.g. diabetes, cardiovascular disease, asthma, Alzheimer’s disease, and several forms of cancer). Growing evidence supports that the common denominator of these pathologic conditions is obesity induced low-grade inflammation. Our team’s research efforts concentrate on the interplay between immunological and metabolic processes which has recently been defined as immunometabolism; an emerging field of investigation at the interface between the historically distinct disciplines of immunology and metabolism. More specifically, our research focuses on the recently described role of adipose tissue T cells in the development of obesity-associated insulin resistance and type-2 diabetes. In particular, we are investigating the role of the ligand-activated nuclear receptor transcription factor Peroxisome Proliferator-Activated Receptor Beta (PPARbeta) in T cell biology in this context. We use both in vitro and in vivo models to study the role of PPARbeta in T cell proliferation/polarization, metabolism, mitochondria biogenesis/function, and oxidative stress. From these studies, we anticipate to obtain a better knowledge of the cellular and molecular mechanisms implicated in metabolic dysfunctions in obese/insulin resistant patients and to identify new targets for novel therapeutic approaches. Figure: T cell staining (CD3) showing adipose tissue from an obese mouse with several adipocytes surrounded by T cells.
Major Publications
2014 Neels JG, Grimaldi PA. Physiological functions of peroxisome proliferator-activated receptor β. Physiol Rev. 2014 Jul;94(3):795-858 2013 Neels JG. A role for 5-lipoxygenase products in obesity-associated inflammation and insulin resistance. Adipocyte. 2013 Oct 1;2(4):262-5. 2012 Salles J, Tardif N, Landrier JF, Mothe-Satney I, Guillet C, Boue-Vaysse C, Combaret L, Giraudet C, Patrac V, Bertrand-Michel J, Denis P, Chardigny JM, Boirie Y, Walrand S. TNFα gene knockout differentially affects lipid deposition in liver and skeletal muscle of high-fat-diet mice. J Nutr Biochem. 2012 Dec;23(12):1685-93. Mothe-Satney I, Filloux C, Amghar H, Pons C, Bourlier V, Galitzky J, Grimaldi PA, Féral CC, Bouloumié A, Van Obberghen E, Neels JG. Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin resistance in mice. Diabetes. 2012 Sep;61(9):2311-9. Zeanandin G, Molato O, Le Duff F, Guerin O, Hebuterne X, Schneider SM: Impact of restrictive diets on the risk of undernutrition in a free-living elderly population. Clin Nutr 2012;31:69-73 Zeanandin G, Balage M, Schneider SM, Dupont J, Hebuterne X, Mothe-Satney I, Dardevet D: Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach. Age (Dordr) 2012;34:371-387 Vanbiervliet G, Filippi J, Karimdjee BS, Venissac N, Iannelli A, Rahili A, Benizri E, Pop D, Staccini P, Tran A, Schneider S, Mouroux J, Gugenheim J, Benchimol D, Hebuterne X: The role of clips in preventing migration of fully covered metallic esophageal stents: a pilot comparative study. Surg Endosc 2012;26:53-59 2011 Whelan K, Schneider SM: Mechanisms, prevention, and management of diarrhea in enteral nutrition. Curr Opin Gastroenterol 2011;27:152-159 Tardif N, Salles J, Landrier JF, Mothe-Satney I, Guillet C, Boue-Vaysse C, Combaret L, Giraudet C, Patrac V, Bertrand-Michel J, Migne C, Chardigny JM, Boirie Y, Walrand S: Oleate-enriched diet improves insulin sensitivity and restores muscle protein synthesis in old rats. Clin Nutr 2011;30:799-806 Preiser JC, Schneider SM: ESPEN disease-specific guideline framework. Clin Nutr 2011;30:549-552 Palasuwan A, Suksom D, Margaritis I, Soogarun S, Rousseau AS: Effects of tai chi training on antioxidant capacity in pre- and postmenopausal women. J Aging Res 2011;2011:234696 Palasuwan A, Margaritis I, Soogarun S, Rousseau AS: Dietary intakes and antioxidant status in mind-body exercising pre- and postmenopausal women. J Nutr Health Aging 2011;15:577-584 Lendoye E, Sibille B, Rousseau AS, Murdaca J, Grimaldi PA, Lopez P: PPARbeta activation induces rapid changes of both AMPK subunit expression and AMPK activation in mouse skeletal muscle. Mol Endocrinol 2011;25:1487-1498 Crispim SP, Geelen A, Souverein OW, Hulshof PJ, Ruprich J, Dofkova M, Huybrechts I, De Keyzer W, Lillegaard IT, Andersen LF, Lafay L, Rousseau AS, Ocke MC, Slimani N, van 't Veer P, de Vries JH: Biomarker-based evaluation of two 24-h recalls for comparing usual fish, fruit and vegetable intakes across European centers in the EFCOVAL Study. Eur J Clin Nutr 2011;65 Suppl 1:S38-47 Crispim SP, de Vries JH, Geelen A, Souverein OW, Hulshof PJ, Lafay L, Rousseau AS, Lillegaard IT, Andersen LF, Huybrechts I, De Keyzer W, Ruprich J, Dofkova M, Ocke MC, de Boer E, Slimani N, van't Veer P: Two non-consecutive 24 h recalls using EPIC-Soft software are sufficiently valid for comparing protein and potassium intake between five European centres--results from the European Food Consumption Validation (EFCOVAL) study. Br J Nutr 2011;105:447-458 Belouze M, Sibille B, Rey B, Roussel D, Romestaing C, Teulier L, Baetz D, Koubi H, Servais S, Duchamp C: Leanness of Lou/C rats does not require higher thermogenic capacity of brown adipose tissue. Physiol Behav 2011;104:893-899 Balage M, Dupont J, Mothe-Satney I, Tesseraud S, Mosoni L, Dardevet D: Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance. J Nutr Biochem 2011;22:219-226 2010 Yandza T, Schneider SM, Novellas S, Badan L, Saint-Paul MC, Bounin PA, Rahili A, Zeanandin G, Benchimol D, Gugenheim J, Hebuterne X: Esophageal varices in chronic intestinal insufficiency in absence of portal hypertension or liver cirrhosis: case report. Transplant Proc 2010;42:103-105 Yandza T, Schneider SM, Nishida S, Goubaux B, Badan L, Vanbiervliet G, Saint-Paul MC, Bernard G, Laffont C, Gari-Toussaint M, Girard-Pipau F, Miton V, Rahili A, Zeanandin G, Benchimol D, Tzakis A, Gugenheim J, Hebuterne X: Outcome of exfoliative rejection after isolated intestinal transplantation in an adult: case report. Transplant Proc 2010;42:100-102 Schindler K, Pernicka E, Laviano A, Howard P, Schutz T, Bauer P, Grecu I, Jonkers C, Kondrup J, Ljungqvist O, Mouhieddine M, Pichard C, Singer P, Schneider S, Schuh C, Hiesmayr M: How nutritional risk is assessed and managed in European hospitals: a survey of 21,007 patients findings from the 2007-2008 cross-sectional nutritionDay survey. Clin Nutr 2010;29:552-559 Rey B, Roussel D, Romestaing C, Belouze M, Rouanet JL, Desplanches D, Sibille B, Servais S, Duchamp C: Up-regulation of avian uncoupling protein in cold-acclimated and hyperthyroid ducklings prevents reactive oxygen species production by skeletal muscle mitochondria. BMC Physiol 2010;10:5 Muscaritoli M, Anker SD, Argiles J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, Fearon KC, Laviano A, Maggio M, Rossi Fanelli F, Schneider SM, Schols A, Sieber CC: Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics". Clin Nutr 2010;29:154-159 Michiels JF, Perrin C, Leccia N, Massi D, Grimaldi P, Wagner N: PPARbeta activation inhibits melanoma cell proliferation involving repression of the Wilms' tumour suppressor WT1. Pflugers Arch 2010;459:689-703 Grimaldi PA: Metabolic and nonmetabolic regulatory functions of peroxisome proliferator-activated receptor beta. Curr Opin Lipidol 2010;21:186-191 Eyenga P, Lhuillier F, Morel J, Roussel D, Sibille B, Letexier D, Cespuglio R, Duchamp C, Goudable J, Bricca G, Viale JP: Time course of liver nitric oxide concentration in early septic shock by cecal ligation and puncture in rats. Nitric Oxide 2010;23:194-198 Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M: Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412-423 Chapman J, Miles PD, Ofrecio JM, Neels JG, Yu JG, Resnik JL, Wilkes J, Talukdar S, Thapar D, Johnson K, Sears DD: Osteopontin is required for the early onset of high fat diet-induced insulin resistance in mice. PLoS One 2010;5:e13959

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