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Obesity

Current therapeutic strategies against obesity aim to restrict caloric intake and / or energy expenditure, but current treatments are far from being effective. The discovery of thermogenic brown and beige adipose tissue in human has opened up new potential avenues to combat obesity and its complications. This process of energy dissipation through adipose tissue is tightly regulated, and the elucidation of its regulatory network is a key point for development of new therapeutic approaches.
The group has a research line in which the effect of microRNAs on the expansion of adipose tissue and its functionality is studied, and specifically on
the induction of thermogenesis in brown tissue and browning of white adipose tissue. Another research line of the group studies the specific targeting of drugs promoting browning and thermogenesis to adipose tissue, through nanosystems technology.
Obesity, in addition to being associated with metabolic diseases, is also one of
the primary causes of mental illness. In fact, the prevalence of mental illness in the obese population is high. Our group also investigates the causes of this
relationship and, specifically, how alterations in the expansion and functionality of adipose tissue, through factors secreted into the blood, affect brain processes such as neurogenesis.

PRINCIPAL INVESTIGATOR

Rajaa El Bekay
UGC Endocrinología y Nutrición. IBIMA. CIBERDEM

Sótano Hospital Civil (Hospital Regional Universitario de Málaga)
29009-Málaga

Contact

Ongoing and finished grants in the last five years

Estudio del efecto del complejo microRNA21-nanopartículas de oro sobre el browning. Una estrategia terapéutica para la obesidad y la resistencia a la insulina.

INVESTIGADOR PRINCIPAL: Rajaa El Bekay

DURACIÓN: 01/01/2019 – 31/12/2021 PRESUPUESTO: 99.300,00€

FINANCIADO POR: Instituto de Salud Carlos III

Estudio epigenético, transcriptómico y proteómico de la angiogénesis del tejido adiposo. y su relación con la obesidad y la resistencia a la insulina.

INVESTIGADOR PRINCIPAL: Rajaa El Bekay

DURACIÓN: 01/09/2013 – 30/09/2017 PRESUPUESTO: 233.242,00€

FINANCIADO POR: Consejería de Innovacion Junta de Andalucía

La Angiogénesis como factor Limitante de la expansión del Tejido Adiposo. Relación con la obesidad y la resistencia a la insulina.

INVESTIGADOR PRINCIPAL: Rajaa El Bekay 

DURACIÓN: 01/01/2014 – 30/06/2017 PRESUPUESTO: 115.555,00€

FINANCIADO POR: Instituto de Salud Carlos III

Collaborators

Relevant publications

Gentile AM, Lhamyani S, Coín-Aragüez L, Clemente-Postigo M, Oliva Olivera W, Romero-Zerbo SY, García-Serrano S, García-Escobar E, Zayed H, Doblado E, Bermúdez-Silva FJ, Murri M, Tinahones FJ, El Bekay R. miR-20b, miR-296, and Let-7f Expression in Human Adipose Tissue is Related to Obesity and Type 2 Diabetes. Obesity (Silver Spring). 2019 Feb;27(2):245-254. doi:10.1002/oby.22363. Epub 2018 Dec 30. PubMed PMID: 30597763.
Coín-Aragüez L, Pavón FJ, Contreras A, Gentile AM, Lhamyani S, De Diego-Otero Y, Casado Y, Oliva Olivera W, Olveira G, Tinahones FJ, Pérez Costillas L, El Bekay R. Inflammatory gene expression in adipose tissue according to diagnosis of anxiety and mood disorders in obese and non-obese subjects. Sci Rep. 2018 Nov30;8(1):17518. doi: 10.1038/s41598-018-35759-9. PubMed PMID: 30504920; PubMed Central PMCID: PMC6269530.
Oliva-Olivera W, Lhamyani S, Coín-Aragüez L, Alcaide-Torres J, Cardona F, El Bekay R, Tinahones FJ. Involvement of acetyl-CoA-producing enzymes in the deterioration of the functional potential of adipose-derived multipotent cells from subjects with metabolic syndrome. Metabolism. 2018 Nov;88:12-21. doi: 10.1016/j.metabol.2018.08.004. Epub 2018 Aug 31. PubMed PMID: 30172756.
Oliva-Olivera W, Moreno-Indias I, Coín-Aragüez L, Lhamyani S, Alcaide Torres J, Fernández-Veledo S, Vendrell J, Camargo A, El Bekay R, Tinahones FJ. Different response to hypoxia of adipose-derived multipotent cells from obese subjects with and without metabolic syndrome. PLoS One. 2017 Nov 22;12(11):e0188324. doi:10.1371/journal.pone.0188324. eCollection 2017. PubMed PMID: 29166648; PubMed Central PMCID: PMC5699836.
Oliva-Olivera W, Coín-Aragüez L, Lhamyani S, Salas J, Gentile AM, Romero-Zerbo SY, Zayed H, Valderrama J, Tinahones FJ, El Bekay R. Differences in the neovascular potential of thymus versus subcutaneous adipose-derived stem cells from patients with myocardial ischaemia. J Tissue Eng Regen Med. 2018 Mar;12(3):e1772-e1784. doi: 10.1002/term.2585. Epub 2018 Jan 3. PubMed PMID: 29024495.
El Bekay R, Coín-Aragüez L, Fernández-García D, Oliva-Olivera W, Bernal-López R, Clemente-Postigo M, Delgado-Lista J, Diaz-Ruiz A, Guzman-Ruiz R, Vázquez-Martínez R, Lhamyani S, Roca-Rodríguez MM, Veledo SF, Vendrell J, Malagón MM, Tinahones FJ. Effects of glucagon-like peptide-1 on the differentiation and metabolism of human adipocytes. Br J Pharmacol. 2016 Jun;173(11):1820-34. doi: 10.1111/bph.13481. Epub 2016 Apr 28. PubMed PMID: 26993859; PubMed Central PMCID:PMC4867741.
Roca-Rodríguez MM, El Bekay R, Garrido-Sanchez L, Gómez-Serrano M, Coin-Aragüez L, Oliva-Olivera W, Lhamyani S, Clemente-Postigo M, García-Santos E, de Luna Diaz R, Yubero-Serrano EM, Fernández Real JM, Peral B, Tinahones FJ. Parathyroid Hormone-Related Protein, Human Adipose-Derived Stem Cells Adipogenic Capacity and Healthy Obesity. J Clin Endocrinol Metab. 2015 Jun;100(6):E826-35. doi: 10.1210/jc.2014-4132. Epub 2015 Apr 17. PubMed PMID: 25885945.
Tinahones FJ, Coín Aragüez L, Murri M, Oliva Olivera W, Mayas Torres MD, Barbarroja N, Gomez Huelgas R, Malagón MM, El Bekay R. Caspase induction and BCL2 inhibition in human adipose tissue: a potential relationship with insulin signaling alteration. Diabetes Care. 2013 Mar;36(3):513-21. doi: 10.2337/dc12-0194. Epub 2012 Nov 27. PubMed PMID: 23193206; PubMed Central PMCID:PMC3579349.
Díaz-Ruiz A, Guzmán-Ruiz R, Moreno NR, García-Rios A, Delgado-Casado N, Membrives A, Túnez I, El Bekay R, Fernández-Real JM, Tovar S, Diéguez C, Tinahones FJ, Vázquez-Martínez R, López-Miranda J, Malagón MM. Proteasome Dysfunction Associated to Oxidative Stress and Proteotoxicity in Adipocytes Compromises Insulin Sensitivity in Human Obesity. Antioxid Redox Signal. 2015 Sep 1;23(7):597-612. doi: 10.1089/ars.2014.5939. Epub 2015 Mar 31. PubMed PMID: 25714483; PubMed Central PMCID: PMC4554552.
Abdel-Motal UM, G A, Abdelalim EM, Ponnuraja C, Iken K, Jahromi M, Doss GP, El Bekay R, Zayed H. Prevalence of nephropathy in type 1 diabetes in the Arab world: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2018 Oct;34(7):e3026. doi: 10.1002/dmrr.3026. Epub 2018 Jun 8. PubMed PMID: 29774648.

Available Tecniques

– Isolation, phenotyping, culture and differentiation of mesenchimal stem cells derived from adipose tissue to white, beige and brown adipocytes, osteocytes and endothelial cells
– Tissue culture of adipose and brain, cell lines and primary culture of human, mouse and rat adipocytes, peripheral cells and macrophages
– Studies in animal models (rat and mouse) of obesity and insulin resistance
– RT qPCR, Western Blot, Immunohistochemistry, immunofluorescence and electron microscopy.
– Analysis of DNA-protein interaction by EMSA assay
– Analysis of epigenetic changes (miRNAs and DNA methylation)
– Analysis of oxidative stress in vitro
– Bioinformatic analysis of miRNAs (function, target genes) by Mirtabase,
DAVID, PANTHER, Cytoscape software