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MOLECULAR METABOLISM AND DISEASE

Department of Biochemistry and Molecular Biomedicine Faculty of Biology. University of Barcelona

Our research group is focused on the study of the molecular and physiological basis of control of energy metabolism, and how it relates to human pathologies. We study the molecular mechanisms of brown, beige and white adipocyte plasticity, as well as muscle and hepatic metabolism. Molecular actors conveying new metabolic and endocrine functions of cells, tissues and organs are identified and characterized. Identification of the signaling molecules determining cellular and organ cross-talk is a main research subject.

LATEST NEWS


Since the affiliation of our research team at Institut de Recerca Sant Joan de Deu, a fruitful program of collaborative research in pediatric endocrinology has developed with the team leaded by Dr. Lourdes Ibàñez. Recent results on the importance of sex differences in brown fat activity in the first year of life and the role of the batokine CXCL14 have been presented at the III IRSJD Scientific Meeting  held at Facultat de Biologia, University of Barcelona, the last  October, 28 These results have been recently published at J Clin Endocr Metab.



 




Obesity is expanding in dogs leading to disease conditions in these domestic pets and affecting their quality of life and that from their owners. Moreover, management of obesity in pets has relevant economic implications. F.Villarroya participated as invited speaker in the on-line symposium with a presentation on the mechanisms involved in the pathogenic consequences of hypertrophied fat, plasticity of adipose tissue and evidence of these phenomena in dogs.

 




The event of presentation of Sanna Laurila thesis, from the PET laboratory at the University of Turku, took place last 13 August, with Francesc Villarroya acting as opponent, a honorary role for doctorate qualification in the Finish University. The work by S.Laurila was related to the role of secretin in the control of human brown adipose tissue activity and was developed in the laboratory of K.Virtanen and P.Nuutila, international leader in research on human brown fat.





In line with our affiliation to Institut de Recerca Sant Joan de Déu (IRSJD), we participated in a study published recently in Science Translational Medicine (DOI: 10.1126/scitranslmed.abb0322), the prestigious journal from the Science group. This research, led by Dr. Carles Lerin at IRSJD, identified an inverse relationship between maternal breast milk betaine content and infant growth, and it was demonstrated that  maternal betaine supplementation during lactation induced a transient increase in offspring intestinal Akkermansia abundance, and reduced early weight gain. Furthermore, it was shown that maternal betaine supplementation decreased adiposity and improved glucose metabolism throughout adulthood, demonstrating a link between breast milk betaine content and long-term metabolic health. Our participation in this study is a follow up of  our long standing research on the molecular basis of the healthy properties of breastfeeding.
A recent article  (https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000918) published in PLOS Biology, presents a list of the 2% of scientists worldwide that lead different disciplines. This ranking has been conducted with the information provided by the Scopus database. Francesc Villarroya appears as one of these top 2% influential researchers in field of Endocrinology and Metabolism.
Albert Mestres Arenas, PhD student at our team, has been awarded by "Comissió de dinamització Lingüística de la Facultat de Biologia UB" with the prize to the best graduation thesis document written in Catalan (academic year 2019-20) for his work “Caracterització fenotípica del teixit adipós perivascular aòrtic i estudi comparatiu amb altres dipòsits adiposos”, developed at our laboratory. Congratulations!
The "Institut de Recerca Sant Joan de Déu" (IRSJD) has been recognized by the Board of Trustees of the Institution of the Research Centers of Catalonia (CERCA) as a CERCA center. This  implies the recognition of the frontier biomedical research developed at IRSJD and oriented to the improvement of quality of life in children and adults. The CERCA recognition implies entering the Catalan research structure, as a top quality research center showing efficient management, and will allow access to additional funds to develop scientific activities.

Our research team has been part of IRSJD for a few years, which has enhanced our translational research in metabolism and endocrinology in collaboration with clinics at Sant Joan de Déu hospital. Examples of our translational research in pediatrics follow:


Reduced circulating levels of chemokine CXCL14 in adolescent girls with polycystic ovary syndrome: normalization after insulin sensitization.
García-Beltran C, Cereijo R, Quesada-López T, Malpique R, López-Bermejo A, de Zegher F, Ibáñez L, Villarroya F.
BMJ Open Diabetes Res Care. 2020 Feb;8(1):e001035.

Circulating growth-and-differentiation factor-15 in early life: relation to prenatal and postnatal growth and adiposity measurements.
Díaz M, Campderrós L, Guimaraes MP, López-Bermejo A, de Zegher F, Villarroya F, Ibáñez L.
Pediatr Res. 2020 Apr;87(5):897-902.

Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy.
Dominguez-Gonzalez C, Badosa C, Madruga-Garrido M, Martí I, Paradas C, Ortez C, Diaz-Manera J, Berardo A, Alonso-Pérez J, Trifunov S, Cuadras D, Kalko SG, Blázquez-Bermejo C, Cámara Y, Martí R, Mavillard F, Martin MA, Montoya J, Ruiz-Pesini E, Villarroya J, Montero R, Villarroya F, Artuch R, Hirano M, Nascimento A, Jimenez-Mallebrera C.
Sci Rep. 2020 Jun 22;10(1):10111.


Brown adipose tissue in prepubertal children: associations with sex, birthweight, and metabolic profile.
Malpique R, Gallego-Escuredo JM, Sebastiani G, Villarroya J, López-Bermejo A, de Zegher F, Villarroya F, Ibáñez L.
Int J Obes (Lond). 2019 Feb;43(2):384-391.



The  Integrase Strand Transfer Inhibitor (INSTI) antiretrovirals are  among the last generation drugs to treat HIV-infected patients. Recent data indicate that these patients show abnormally increased adiposity after treatment. Thus, the HIV infection and global obesity epidemics meet to confer to HIV patients increased metabolic and cardiovascular comorbidities.The coordinated research projects  will assess the molecular and cellular basis of such phenomenon and will identify potential targets of preventive intervention.



That system, in which bradykinin is a main actor, has been traditionally associated with the physiology of the renal and cardiovascular systems and processes of inflammation and pain. Our study, led by Dr.M.Peyrou, Juan de la Cierva researcher at our lab, reports that the kallikrein-kinin system acts as mechanism of molecular self-control of brown and beige adipose tissue thermogenic activation, and could help prevent the harmful effects of excessive activation of brown adipose tissue occurring in some pathological conditions such as cachexia or recovery from severe burns.The full article is accessible at:   https://rdcu.be/b3Ud4



A project on hepatocarcinogenesis and metabolic lipotoxity, led by Francesc
Villarroya, has been one of the initiatives selected by the AECC, in the category of Ideas Semilla 2019. F. Villarroya was in charge of representing the project in the commemorative act that the AECC held on September 24, in the Reina Sofía Museum in Madrid, on the occasion of World Research Day in Cancer (World Cancer Research Day).
In this edition, the AECC Scientific Foundation Research programs awarded 171 projects worth about 21 million euros, which integrate from great innovative and disruptive ideas to projects financed in a coordinated manner with large European foundations. Our focus is to investigate whether brown fat activation could be protective against liver cancer, as preliminary studies in our laboratory suggest. 



Expertscape is an international web-based data analysis algorithm  that  objectively ranks people and and institutions by their expertise in more than 27,000 biomedical topics, based on  scientific publications. For details see:    http://www.expertscape.com/ex/adipose+tissue



Ruben Cereijo is a post-doctoral researcher, assistant professor at UB, member of our research team. The “Societat Catalana de Biologia” Young Researcher Award is for his doctoral thesis “Nous actors moleculars en la fisiologia del teixit adipós i pathologies associades”, read in the University of Barcelona in 2015, and the award to the best article is for the paper “CXCL14, a brown adipokine that mediates brown-fat-to-macrophage communication in thermogenic adaptation”, published in the prestigious scientific journal Cell Metabolism in 2018  (https://www.ncbi.nlm.nih.gov/pubmed/30122557). According to this study, the CXCL14 protein –formerly related to tumor progression and organogenesis- is synthetized by the brown adipose tissue and can activate cells with anti-inflammatory activity –M2 macrophages-, which have beneficial effects on metabolism and protect against type II diabetes and obesity. The prizes were given to the winners in the ceremony of the 4th Night of Biology, held in the Ramon Margalef Auditorium of CosmoCaixa Barcelona on July 10. Further information can be found at: https://www.ub.edu/dyn/cms/continguts_ca/menu_eines/noticies/index.html



The Adipoplast network organized an open symposium on "The adipose tissue plasticity in health and disease" followed by an internal organizational meeting at "Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS)", Santiago de Compostela, the last March 12th. Members of the Adipoplast network presented recent research advances as well as collaborative perspectives. External speakers were the international reputed scientists on adipobiology Dr L.Fajas (University of Lausanne, Switzerland) and Dr. R. Nogueiras (CIMUS). More than forty attendants participated. Plans for further actions were developed in the Adipoplast organizational meeting. Adipoplast is a "Red de Excelencia" supported by the Spanish government to promote interdisciplinary research on adipose tissue, and is coordinated by Francesc Villarroya.


Dr Ruben Cereijo is coordinating this activity at our stand in the Fair.

The Live Research Fair is a forum organized by the Barcelona Science Park (PCB) and Obra Social la Caixa which gather research groups from Catalan institutions to create a communication space for science and society –beyond the and research atmosphere- and promote scientific vocations among youngsters. The Live Research Fair is part of the science dissemination program of PCB’s Recerca en Societat. This year, from March 6 to 9, attendants will see the relationship between the active brown fat and a good metabolic health through the assessment of brown fat activity through infrared thermography.


LAST PUBLICATIONS

The endocrine role of brown adipose tissue: An update on actors and actions.

Aleix Gavaldà-Navarro, Joan Villarroya, Rubén Cereijo, Marta Giralt, Francesc Villarroya

Rev Endocr Metab Disord . 2021 Mar 12. doi: 10.1007/s11154-021-09640-6.

In recent years, brown adipose tissue (BAT) has been recognized not only as a main site of non-shivering thermogenesis in mammals, but also as an endocrine organ. BAT secretes a myriad of regulatory factors. These so-called batokines exert local autocrine and paracrine effects, as well as endocrine actions targeting tissues and organs at a distance. The endocrine batokines include peptide factors, such as fibroblast growth factor-21 (FGF21), neuregulin-4 (NRG4), phospholipid transfer protein (PLTP), interleukin-6, adiponectin and myostatin, and also lipids (lipokines; e.g., 12,13-dihydroxy-9Z-octadecenoic acid [12,13-diHOME]) and miRNAs (e.g., miR-99b). The liver, heart, and skeletal muscle are the most commonly reported targets of batokines. In response to BAT thermogenic activation, batokines such as NRG4 and PLTP are released and act to reduce hepatic steatosis and improve insulin sensitivity. Stress-induced interleukin-6-mediated signaling from BAT to liver favors hepatic glucose production through enhanced gluconeogenesis. Batokines may act on liver to induce the secretion of regulatory hepatokines (e.g. FGF21 and bile acids in response to miR-99b and PLTP, respectively), thereby resulting in a systemic expansion of BAT-originating signals. Batokines also target extrahepatic tissues: FGF21 and 12,13-diHOME are cardioprotective, whereas BAT-secreted myostatin and 12,13-diHOME influence skeletal muscle development and performance. Further research is needed to ascertain in humans the role of batokines, which have been identified mostly in experimental models. The endocrine role of BAT may explain the association between active BAT and a healthy metabolism in the human system, which is characterized by small amounts of BAT and a likely moderate BAT-mediated energy expenditure.

CONTACT US

  • 934021523 / 606148772
  • g.moreno@ub.edu
  • Departament de Bioquímica i Biomedicina Molecular.
    Facultat de Biologia (UB)
    Avda. Diagonal, 645
    Edifici nou Pl. -1
    08028 Barcelona

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