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

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

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

adipogenesis: human cellular models and molecular aspects. - 2012 - Biochim Biophys Acta - 1831 P905-14 - Beranger GE, Karbiener M, Barquissau V, Pisani DF, Scheideler M, Langin D, and Amri,EZ

Activation of protein kinase A and exchange protein directly activated by cAMP promotes adipocyte differentiation of human mesenchymal stem cells. - 2012 - PLoS One - 7 Pe34114 - Jia B, Madsen L, Petersen RK, Techer N, Kopperud R, Ma T, D SO, í¸skeland G, Ailhaud J, Wang EZ, Amri K, and Kristiansen,

Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. - 2012 - J Clin Invest - 122 P1022-36 - Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dess P, í¬-Fulgheri C, Zhang N, Takahashi R, Sarzani S, and Collins,

β₁-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β₃-adrenergic receptor-knockout mice via nonshivering thermogenesis. - 2011 - American journal of physiology. Endocrinology and metabolism - 301 PE1108-18 - Mattsson CL, Csikasz RI, Chernogubova E, Yamamoto DL, Hogberg HT, Amri EZ, Hutchinson DS, and Bengtsson,T

Oxytocin and bone remodelling: relationships with neuropituitary hormones, bone status and body composition. - 2011 - Joint Bone Spine - 78 P611-5 - Breuil V, Amri EZ, Panaia-Ferrari P, Testa J, Elabd C, Albert-Sabonnadi C, ère CH, Roux G, Ailhaud C, Dani GF, Carle L, and Euller-Ziegler,

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Amri Ez-Zoubir
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CNRS UMR7277, Inserm U1091, UNS Université Nice Sophia Antipolis
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