Zoubir AMRI
Cellular and Molecular Regulation of Fat Mass
Main interests
- Deciphering the mechanisms of Brite adipocyte formation and activation
- Nutritional control of white adipocyte browning
- Adipocyte/hepatocyte cross talk
- Oxytocin prevents Obesity and Osteoporosis
Scientific Questions
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 Strategy
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.
Research Aims
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.
Researchers
ROCHET Nathalie - +33 489153702
SATNEY Isabelle - +33 489153709
SIBILLE Brigitte - +33 489153704
ROUSSEAU Anne-Sophie - +33 489153704
Clinical Researchers
BALAGUER Thierry - +33 492033853
ROUX Christian - +33 489153704
PreDocs
BATROW Pierre-Louis - +33 489153704
CONTU Laura - +33 489153704
MERCIER Julien - +33 489153704
Engineers & Technicians
GAUTIER Nadine - +33 489153703
Recent publications
- Díez-Sainz, E, Aranaz, P, Amri, EZ, Riezu-Boj, JI, Lorente-Cebrián, S, Milagro, FI et al.. Plant miR8126-3p and miR8126-5p Decrease Lipid Accumulation through Modulation of Metabolic Genes in a Human Hepatocyte Model That Mimics Steatosis. Int J Mol Sci. 2024;25 (3):. doi: 10.3390/ijms25031721. PubMed PMID:38338999 PubMed Central PMC10855419.
- Sanchez, C, Colson, C, Gautier, N, Noser, P, Salvi, J, Villet, M et al.. Dietary fatty acid composition drives neuroinflammation and impaired behavior in obesity. Brain Behav Immun. 2024;117 :330-346. doi: 10.1016/j.bbi.2024.01.216. PubMed PMID:38309640 .
- Batrow, PL, Mothe-Satney, I, Amri, EZ. [Thermoneutrality and animal study]. Med Sci (Paris). 2023;39 (12):937-944. doi: 10.1051/medsci/2023176. PubMed PMID:38108724 .
- Díez-Sainz, E, Lorente-Cebrián, S, Aranaz, P, Amri, EZ, Riezu-Boj, JI, Milagro, FI et al.. miR482f and miR482c-5p from edible plant-derived foods inhibit the expression of pro-inflammatory genes in human THP-1 macrophages. Front Nutr. 2023;10 :1287312. doi: 10.3389/fnut.2023.1287312. PubMed PMID:38099184 PubMed Central PMC10719859.
- Lambeau, G, Amri, EZ, Carrière, F. Lipids play music at the cellular membrane: From membranes dynamics to signaling via lipid mediators, vesicles and lipid droplets. Biochimie. 2023;215 :1-3. doi: 10.1016/j.biochi.2023.11.002. PubMed PMID:38000848 .
- U-Din, M, de Mello, VD, Tuomainen, M, Raiko, J, Niemi, T, Fromme, T et al.. Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD+ metabolism in humans. Cell Rep. 2023;42 (9):113131. doi: 10.1016/j.celrep.2023.113131. PubMed PMID:37708023 .
- Roux, CH, Rousseau, AS, Iannelli, A, Gautier, N, Ferrero, S, Hinault, C et al.. The Association between Oxytocin and Lower Limb Osteoarthritis: A Prospective Cohort Study. Int J Mol Sci. 2023;24 (11):. doi: 10.3390/ijms24119750. PubMed PMID:37298701 PubMed Central PMC10254062.
- Colson, C, Batrow, PL, Dieckmann, S, Contu, L, Roux, CH, Balas, L et al.. Effects of Fatty Acid Metabolites on Adipocytes Britening: Role of Thromboxane A2. Cells. 2023;12 (3):. doi: 10.3390/cells12030446. PubMed PMID:36766790 PubMed Central PMC9913700.
- Fougerat, A, Schoiswohl, G, Polizzi, A, Régnier, M, Wagner, C, Smati, S et al.. ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity. Cell Rep. 2022;39 (10):110910. doi: 10.1016/j.celrep.2022.110910. PubMed PMID:35675775 .
- Kornmueller, K, Amri, EZ, Scheideler, M, Prassl, R. Delivery of miRNAs to the adipose organ for metabolic health. Adv Drug Deliv Rev. 2022;181 :114110. doi: 10.1016/j.addr.2021.114110. PubMed PMID:34995679 .
- Balazova, L, Balaz, M, Horvath, C, Horváth, Á, Moser, C, Kovanicova, Z et al.. GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1. Nat Commun. 2021;12 (1):7144. doi: 10.1038/s41467-021-27442-x. PubMed PMID:34880217 PubMed Central PMC8655035.
- Wu, H, Pula, T, Tews, D, Amri, EZ, Debatin, KM, Wabitsch, M et al.. microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis. Cells. 2021;10 (11):. doi: 10.3390/cells10113205. PubMed PMID:34831427 PubMed Central PMC8625276.
- Napolitano, T, Avolio, F, Silvano, S, Forcisi, S, Pfeifer, A, Vieira, A et al.. Gfi1 Loss Protects against Two Models of Induced Diabetes. Cells. 2021;10 (11):. doi: 10.3390/cells10112805. PubMed PMID:34831029 PubMed Central PMC8616283.
- Ferrero, S, Amri, EZ, Roux, CH. Relationship between Oxytocin and Osteoarthritis: Hope or Despair?. Int J Mol Sci. 2021;22 (21):. doi: 10.3390/ijms222111784. PubMed PMID:34769215 PubMed Central PMC8584067.
- Bokhari, MH, Halleskog, C, Åslund, A, Boulet, N, Casadesús Rendos, E, de Jong, JMA et al.. Isothermal microcalorimetry measures UCP1-mediated thermogenesis in mature brite adipocytes. Commun Biol. 2021;4 (1):1108. doi: 10.1038/s42003-021-02639-4. PubMed PMID:34548622 PubMed Central PMC8455563.
- Raad, G, Serra, F, Martin, L, Derieppe, MA, Gilleron, J, Costa, VL et al.. Paternal multigenerational exposure to an obesogenic diet drives epigenetic predisposition to metabolic diseases in mice. Elife. 2021;10 :. doi: 10.7554/eLife.61736. PubMed PMID:33783350 PubMed Central PMC8051948.
- Dufau, J, Shen, JX, Couchet, M, De Castro Barbosa, T, Mejhert, N, Massier, L et al.. In vitro and ex vivo models of adipocytes. Am J Physiol Cell Physiol. 2021;320 (5):C822-C841. doi: 10.1152/ajpcell.00519.2020. PubMed PMID:33439778 .
- Maurer, SF, Dieckmann, S, Lund, J, Fromme, T, Hess, AL, Colson, C et al.. No Effect of Dietary Fish Oil Supplementation on the Recruitment of Brown and Brite Adipocytes in Mice or Humans under Thermoneutral Conditions. Mol Nutr Food Res. 2021;65 (2):e2000681. doi: 10.1002/mnfr.202000681. PubMed PMID:33274552 .
- Colson, C, Batrow, PL, Gautier, N, Rochet, N, Ailhaud, G, Peiretti, F et al.. The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes. Cells. 2020;9 (11):. doi: 10.3390/cells9112433. PubMed PMID:33171828 PubMed Central PMC7695189.
- Peiretti, F, Montanari, R, Capelli, D, Bonardo, B, Colson, C, Amri, EZ et al.. A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor γ Binding Properties and Biological Activities. J Med Chem. 2020;63 (21):13124-13139. doi: 10.1021/acs.jmedchem.0c01555. PubMed PMID:33142057 PubMed Central PMC10211484.
2013 - Prix de la Société Française de Nutrition
UCA Annual Award Ceremony 2019: 4 iBV members recognized this year !
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UCA annual Award Ceremony: 7 iBV members recognised for their scientific contributions
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iBV - Institut de Biologie Valrose
"Tour Pasteur"
Université Nice Sophia Antipolis
Faculté de médecine
28 Avenue de Valombrose
06189 Nice cedex 2