Cellular and molecular regulation of fat mass
- Deciphering the mechanisms of Brite adipocyte formation and activation
- Nutritional control of white adipocyte browning
- Adipocyte/hepatocyte cross talk
- Oxytocin prevents Obesity and Osteoporosis
Obesity has reached epidemic proportions world-wide, with more than 2 billion overweight patients among which at least 700 million obese. Moreover, body weight gain and fat mass redistribution represent a major public health problem with aging as a larger proportion of the adult population is at risk of developing obesity and associated diseases. Increase in body mass index is accompanied by an increase in the mass of white adipose tissue (WAT) and results from an imbalance between energy intake and energy expenditure. So far, except bariatric surgery for morbid obese patients, no efficient treatment is available. Thus, development of new pharmacological remedies or lifestyle interventions normalizing this imbalance with significant long-term success will be of great interest.
Our research program is focused on the regulation of fat mass by two complementary approaches whose aims were i) to find new tools to induce the formation and activation of functional brown adipocytes and ii) to control the mass and redistribution of white adipose tissue (WAT). It is now established that healthy adult humans possess active brown adipose tissue (BAT), localized in small depots at various anatomical sites, which control energy expenditure through heat production. The formation of brown adipocytes in WAT (brite/beige) attracts considerable research interest. Using a human cell model (hMADS cells) and human primary cultures combined with in vivo studies (mice) and human biopsies we characterized the process of white to brown/brite adipocyte conversion and identified several key components controlling this step.
We identified OT as a potential hormone that controls the adipocyte/osteoblast balance. OT administration to ovariectomized mice is a preventive and curative treatment of body weight gain, fat mass redistribution and osteoporosis. OT circulating levels are linked to bone mineral density in women but not in men.
Our research program is related to fundamental and medical issues related to obesity and its associated diseases. We aim to advance the understanding of mechanisms underlying the formation and activation of brite adipocytes as well as their cross-talk with other organs, paving a way for the development of innovative treatments.
In the absence of effective and safe pharmaceutical treatments of obesity, the development of nutritional interventions to modulate metabolic functions of adipose tissues are a promising alternative approach. We aim to identify distinct fatty acid metabolites in murine and human adipose tissues, which are associated with brite adipogenesis and thus able to increase energy expenditure.
In addition to their role in adipocyte biology, fatty acid metabolites are considered as mediators of inflammation. Interestingly, little is known about the involvement of brown and brite adipocyte in inflammation. We aim to develop a research program related to inflammation, metabolism and brite/brown adipocytes function.
As adipose tissue interacts with several organs, we will develop a research program studying the crosstalk between white, brown/brite adipocytes and hepatocytes.
Our work on OT will target the role of this hormone in adipocyte and osteoblast formation. We are developing clinical studies in collaboration with Pr. C. Roux, CHU de Nice service Rhumatoloie and Pr. JL Sadoul, CHU Nice and Head of CERON: Centre d’Études et de Recherche sur l’Obésité de Nice Côte d’Azur.
- Leboucher, A, Pisani, DF, Martinez-Gili, L, Chilloux, J, Bermudez-Martin, P, Van Dijck, A et al.. The translational regulator FMRP controls lipid and glucose metabolism in mice and humans. Mol Metab. 2019;21 :22-35. doi: 10.1016/j.molmet.2019.01.002. PubMed PMID:30686771 PubMed Central PMC6407369.
- Balaz, M, Becker, AS, Balazova, L, Straub, L, Müller, J, Gashi, G et al.. Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation. Cell Metab. 2019;29 (4):901-916.e8. doi: 10.1016/j.cmet.2018.11.017. PubMed PMID:30581121 .
- Szulc, P, Amri, EZ, Varennes, A, Panaia-Ferrari, P, Fontas, E, Goudable, J et al.. Positive Association of High Leptin Level and Abdominal Aortic Calcification in Men - The Prospective MINOS Study. Circ. J. 2018;82 (12):2954-2961. doi: 10.1253/circj.CJ-18-0517. PubMed PMID:30282882 .
- Maurer, SF, Dieckmann, S, Kleigrewe, K, Colson, C, Amri, EZ, Klingenspor, M et al.. Fatty Acid Metabolites as Novel Regulators of Non-shivering Thermogenesis. Handb Exp Pharmacol. 2019;251 :183-214. doi: 10.1007/164_2018_150. PubMed PMID:30141101 .
- U Din, M, Saari, T, Raiko, J, Kudomi, N, Maurer, SF, Lahesmaa, M et al.. Postprandial Oxidative Metabolism of Human Brown Fat Indicates Thermogenesis. Cell Metab. 2018;28 (2):207-216.e3. doi: 10.1016/j.cmet.2018.05.020. PubMed PMID:29909972 .
- Babaei, R, Schuster, M, Meln, I, Lerch, S, Ghandour, RA, Pisani, DF et al.. Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis. Sci Signal. 2018;11 (527):. doi: 10.1126/scisignal.aai7838. PubMed PMID:29692363 .
- Balaguer, T, Fellah, BH, Boukhechba, F, Traverson, M, Mouska, X, Ambrosetti, D et al.. Combination of blood and biphasic calcium phosphate microparticles for the reconstruction of large bone defects in dog: A pilot study. J Biomed Mater Res A. 2018;106 (7):1842-1850. doi: 10.1002/jbm.a.36384. PubMed PMID:29573560 .
- Barquissau, V, Léger, B, Beuzelin, D, Martins, F, Amri, EZ, Pisani, DF et al.. Caloric Restriction and Diet-Induced Weight Loss Do Not Induce Browning of Human Subcutaneous White Adipose Tissue in Women and Men with Obesity. Cell Rep. 2018;22 (4):1079-1089. doi: 10.1016/j.celrep.2017.12.102. PubMed PMID:29386128 .
- Lasar, D, Rosenwald, M, Kiehlmann, E, Balaz, M, Tall, B, Opitz, L et al.. Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase. Cell Rep. 2018;22 (3):760-773. doi: 10.1016/j.celrep.2017.12.067. PubMed PMID:29346772 .
- Ghandour, RA, Colson, C, Giroud, M, Maurer, S, Rekima, S, Ailhaud, G et al.. Impact of dietary ω3 polyunsaturated fatty acid supplementation on brown and brite adipocyte function. J. Lipid Res. 2018;59 (3):452-461. doi: 10.1194/jlr.M081091. PubMed PMID:29343538 PubMed Central PMC5832935.
- Pisani, DF, Barquissau, V, Chambard, JC, Beuzelin, D, Ghandour, RA, Giroud, M et al.. Mitochondrial fission is associated with UCP1 activity in human brite/beige adipocytes. Mol Metab. 2018;7 :35-44. doi: 10.1016/j.molmet.2017.11.007. PubMed PMID:29198749 PubMed Central PMC5784321.
- Amri, EZ, Scheideler, M. Small non coding RNAs in adipocyte biology and obesity. Mol. Cell. Endocrinol. 2017;456 :87-94. doi: 10.1016/j.mce.2017.04.009. PubMed PMID:28412522 .
- Abumrad, NA, Amri, EZ, Luquet, S, Forest, C. Pleiotropic physiological roles of PPARs and fatty acids: A tribute to Paul Grimaldi. Biochimie. 2017;136 :1-2. doi: 10.1016/j.biochi.2017.03.016. PubMed PMID:28372706 .
- Barquissau, V, Ghandour, RA, Ailhaud, G, Klingenspor, M, Langin, D, Amri, EZ et al.. Control of adipogenesis by oxylipins, GPCRs and PPARs. Biochimie. 2017;136 :3-11. doi: 10.1016/j.biochi.2016.12.012. PubMed PMID:28034718 .
- Dumortier, O, Roger, E, Pisani, DF, Casamento, V, Gautier, N, Lebrun, P et al.. Age-Dependent Control of Energy Homeostasis by Brown Adipose Tissue in Progeny Subjected to Maternal Diet-Induced Fetal Programming. Diabetes. 2017;66 (3):627-639. doi: 10.2337/db16-0956. PubMed PMID:27927722 .
- Amri, EZ, Pisani, DF. Control of bone and fat mass by oxytocin. Horm Mol Biol Clin Investig. 2016;28 (2):95-104. doi: 10.1515/hmbci-2016-0045. PubMed PMID:27865092 .
- Szulc, P, Amri, EZ, Varennes, A, Panaia-Ferrari, P, Fontas, E, Goudable, J et al.. High serum oxytocin is associated with metabolic syndrome in older men - The MINOS study. Diabetes Res. Clin. Pract. 2016;122 :17-27. doi: 10.1016/j.diabres.2016.09.022. PubMed PMID:27764720 .
- Giroud, M, Pisani, DF, Karbiener, M, Barquissau, V, Ghandour, RA, Tews, D et al.. miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function. Mol Metab. 2016;5 (8):615-625. doi: 10.1016/j.molmet.2016.06.005. PubMed PMID:27656399 PubMed Central PMC5021678.
- Rohm, M, Schäfer, M, Laurent, V, Üstünel, BE, Niopek, K, Algire, C et al.. An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice. Nat. Med. 2016;22 (10):1120-1130. doi: 10.1038/nm.4171. PubMed PMID:27571348 .
- Müller, S, Balaz, M, Stefanicka, P, Varga, L, Amri, EZ, Ukropec, J et al.. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways. Sci Rep. 2016;6 :30030. doi: 10.1038/srep30030. PubMed PMID:27418403 PubMed Central PMC4945940.
2013 - Prix de la Société Française de Nutrition
iBV - Institut de Biologie Valrose
Université Nice Sophia Antipolis
Faculté de médecine
28 Avenue de Valombrose
06189 Nice cedex 2