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

The K+ channel TASK1 modulates β-adrenergic response in brown adipose tissue through the mineralocorticoid receptor pathway. - 2016 - FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 30 P909-22 - Pisani DF, Beranger GE, Corinus A, Giroud M, Ghandour RA, Altirriba J, Chambard JC, Mazure NM, Bendahhou S, Duranton C, Michiels JF, Frontini A, Rohner-Jeanrenaud F, Cinti S, Christian M, Barhanin J, and Amri,EZ

IP-receptor and PPARs trigger the conversion of human white to brite adipocyte induced by carbaprostacyclin. - 2016 - Biochimica et biophysica acta - 1864 P285-93 - Ghandour RA, Giroud M, Vegiopoulos A, Herzig S, Ailhaud G, Amri EZ, and Pisani,DF

Mesoderm-specific transcript (MEST) is a negative regulator of human adipocyte differentiation. - 2015 - International journal of obesity (2005) - 39 P1733-41 - Karbiener M, Glantschnig C, Pisani DF, Laurencikiene J, Dahlman I, Herzig S, Amri EZ, and Scheideler,M

Oxytocin and bone status in men: analysis of the MINOS cohort. - 2015 - Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA - 26 P2877-82 - Breuil V, Fontas E, Chapurlat R, Panaia-Ferrari P, Yahia HB, Faure S, Euller-Ziegler L, Amri EZ, and Szulc,P

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

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Amri Ez-Zoubir
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Members Team
   Ailhaud Gérard
   Chambard Jean-Claude
   Pisani Didier
   Rochet Nathalie
Clinical Researchers
   Roux Christian
   Colson Cécilia
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    September 2016 - Z. Amri Team
   1 PhD position 3 years   Closed



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