Cellular and molecular regulation of fat mass

The increase in the frequency of overweight/obese people has reached a qualified epidemic stage with more than one billion overweight (IMC > 25 kg/m2) and at least 300 millions clinically obese (BMI > 30 kg/m2) with tremendous costs for health care systems. A positive energy balance, which is accompanied by an increase in body weight due to increase in the white adipose tissue mass, is resulting from an imbalance between energy intake and energy expenditure.

There are two types of adipose tissue, white adipose tissue (WAT) and brown adipose tissue (BAT). WAT plays a central role in the control of energy homeostasis. In contrast to WAT BAT is specialized in adaptive thermogenesis in which the uncoupling protein1 plays a key role. In contrast to early contention, healthy adult humans possess BAT with a potential for metabolic significance. Active BAT was found in small amounts in healthy adult human localized in various anatomical sites.

In mice and humans, islands of brown adipocytes emerge within WAT depots after prolonged exposure to a PPARγ ligand, a nuclear receptor of the PPAR family (Peroxisome Proliferator-Activated Receptors). These functional adipocytes, termed “brite” (brown-in-white) adipocytes, are embryologically different from genuine brown adipocytes but are functional. Therefore, the identification of factors leading to increased mass/activity of human BAT are of great interest for the treatment of overweight and obesity as well as for associated diseases.

We set up a unique cellular model (mesenchymal stem cells), i.e. multipotent stem cells derived from human adipose tissue (hMADS cells), which differentiate into white adipocytes and are also able to convert into functional brown (brite) adipocytes upon chronic activation of PPARγ. Our current investigations aim to identify the cellular and molecular mechanisms that underlie the conversion of white to brown adipocytes and to analyze key metabolic pathways and mitochondriogenesis in white versus brown adipocytes.



Last publications

Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers. - 2015 - Genes & development - 29 P7-22 - Loft A, Forss I, Siersbì¦k MS, Schmidt SF, Larsen AS, Madsen JG, Pisani DF, Nielsen R, Aagaard MM, Mathison A, Neville MJ, Urrutia R, Karpe F, Amri EZ, and Mandrup,S

The inward rectifier potassium channel Kir2.1 is required for osteoblastogenesis. - 2015 - Human molecular genetics - 24 P471-9 - Sacco S, Giuliano S, Sacconi S, Desnuelle C, Barhanin J, Amri EZ, and Bendahhou,S

The ω6-fatty acid, arachidonic acid, regulates the conversion of white to brite adipocyte through a prostaglandin/calcium mediated pathway. - 2014 - Molecular metabolism - 3 P834-47 - Pisani DF, Ghandour RA, Beranger GE, Le Faouder P, Chambard JC, Giroud M, Vegiopoulos A, Djedaini M, Bertrand-Michel J, Tauc M, Herzig S, Langin D, Ailhaud G, Duranton C, and Amri,EZ

Oxytocin reverses ovariectomy-induced osteopenia and body fat gain. - 2014 - Endocrinology Pen20131688 - Beranger GE, Pisani DF, Castel J, Djedaini M, Battaglia S, Amiaud J, Boukhechba F, Ailhaud G, Michiels JF, Heymann D, Luquet S, and Amri,EZ

Oxytocin, a new determinant of bone mineral density in post-menopausal women: analysis of the OPUS cohort. - 2014 - J Clin Endocrinol Metab Pjc20134126 - Breuil V, Panaia-Ferrari P, Fontas E, Roux C, Kolta S, Eastell R, Ben Yahia H, Faure S, Gossiel F, Benhamou CL, Euller-Ziegler L, and Amri,EZ

Glucose uptake in brown fat cells is dependent on mTOR complex 2-promoted GLUT1 translocation. - 2014 - The Journal of cell biology - 207 P365-74 - Olsen JM, Sato M, Dallner OS, Sandstrì¶m AL, Pisani DF, Chambard JC, Amri EZ, Hutchinson DS, and Bengtsson,T

Antagonistic functions of LMNA isoforms in energy expenditure and lifespan. - 2014 - EMBO reports - 15 P529-39 - Lopez-Mejia IC, de Toledo M, Chavey C, Lapasset L, Cavelier P, Lopez-Herrera C, Chebli K, Fort P, Beranger G, Fajas L, Amri EZ, Casas F, and Tazi,J

MicroRNA-26 family is required for human adipogenesis and drives characteristics of brown adipocytes. - 2013 - Stem Cells - Karbiener M, Pisani DF, Frontini A, Oberreiter LM, Lang E, Vegiopoulos A, Mössenbí¶ck K, Bernhardt GA, Mayr T, Hildner F, Grillari J, Ailhaud G, Herzig S, Cinti S, Amri EZ, and Scheideler,M

Chondrogenic potential of stem cells derived from adipose tissue: a powerful pharmacological tool. - 2013 - Biochem Biophys Res Commun - 440 P786-91 - Roux C, Pisani DF, Yahia HB, Djedaini M, Beranger GE, Chambard JC, Ambrosetti D, Michiels JF, Breuil V, Ailhaud G, Euller-Ziegler L, and Amri,EZ

Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories. - 2013 - Cell Mol Life Sci - Rieder D, Ploner C, Krogsdam AM, Stocker G, Fischer M, Scheideler M, Dani C, Amri EZ, Müller WG, McNally JG, and Trajanoski,Z

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Amri Ez-Zoubir
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Members Team
   Ailhaud Gérard
   Chambard Jean-Claude
   Pisani Didier
Clinical Researchers
   Roux Christian
   Auverdin Clémence
   Balzo Amanda
   Belgen Anais
   Ghandour Rayane
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