AMRI – iBV

Obesity has reached epidemic proportions world-wide, with more than 2 billion overweight patients among which at least 1 billion patients with obesity. 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. There are some hopes with GLP1 analogues. Thus, development of new pharmacological remedies or lifestyle interventions, such as adapted physical activity, 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. We aim to characterize the metabolic profile of T lymphocytes linked to vitality capacity and the identification of specific protective Treg sub-population(s) in older individuals.

To date, no biomarkers of vitality capacity that could be used in clinic to evaluate the immune-associated protection against lifestyle-related diseases are available. We plan to establish a precise "molecular picture" of T cell metabolic program linked to vitality capacity and health protection, with a focus on Tregs. The originality of our work will be to use the lifelong aerobic exercise and physical inactivity models of aging men and women, as a starting-tool for the determination of a lifestyle-exposure impact on Tregs landscape and functions in health and disease conditions.

Our work on OT will target the role of this hormone in adipocyte, osteoblast and chondrocyte formation. We are developing clinical studies in collaboration with Pr. Christian Roux, CHU de Nice service Rhumatologie and Pr. Antonio Iannelli, CHU de Nice Service de Chirurgie Digestive et Transplantation Hépatique, Co-heads of Adipo-Cible, a consortium supported by the French government, through the UCAJ.E.D.I. Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-15-IDEX-01".

Recent publications

Amri, EZ. Beige or brite adipocytes of the adipose organ: Link with white and brown adipocytes. Ann Endocrinol (Paris). 2024;85 (3):253-254. doi: 10.1016/j.ando.2024.05.002. PubMed PMID:38871507 .
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.
Sibille, B, Mothe-Satney, I, Le Menn, G, Lepouse, D, Le Garf, S, Baudoin, E et al.. Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples. Int J Mol Sci. 2021;22 (21):. doi: 10.3390/ijms222111497. PubMed PMID:34768927 PubMed Central PMC8584242.
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.
Rousseau, AS, Murdaca, J, Le Menn, G, Sibille, B, Wahli, W, Le Garf, S et al.. Invalidation of the Transcriptional Modulator of Lipid Metabolism PPARβ/δ in T Cells Prevents Age-Related Alteration of Body Composition and Loss of Endurance Capacity. Front Physiol. 2021;12 :587753. doi: 10.3389/fphys.2021.587753. PubMed PMID:33815130 PubMed Central PMC8010153.
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.
Le Garf, S, Sibille, B, Mothe-Satney, I, Eininger, C, Fauque, P, Murdaca, J et al.. Alpha-lipoic acid supplementation increases the efficacy of exercise- and diet-induced obesity treatment and induces immunometabolic changes in female mice and women. FASEB J. 2021;35 (4):e21312. doi: 10.1096/fj.202001817RR. PubMed PMID:33742689 .

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Ez-Zoubir AMRI

Cellular and Molecular Regulation of Fat Mass

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Adipo-Cible, a fundamental – translational – clinical research consortium on obesity co-sponsored by iBV!

UCA Annual Award Ceremony 2019: 4 iBV members recognized this year !

UCA annual Award Ceremony: 7 iBV members recognised for their scientific contributions