Metabolic Diseases and Aging

>>Metabolic Diseases and Aging

Obesity is a serious medical problem that involved a high percentage of the world population. Traditionally conceived as a disease of developed countries, it is now recognized as a pandemic by WHO. In Uruguay, nearly 60% of the adult population are considered overweight or obese. Moreover, about 10% of the child population is overweight or obese, and they suffer hypertension and diabetes, pathologies associated with obesity. Understanding the molecular mechanisms involved in pathophysiology of obesity, diabetes and other associated diseases is our main goal. Research aims on Metabolic Diseases and Aging Lab are:

a) to do basic science focused on the molecular mechanisms of metabolic diseases, with a strong emphasis on Sirtuins;

b) To develop novel pharmacological strategies to treat obesity and metabolic diseases.


Paola Contreras

External associated researcher
Faculty of Medicine (Udelar) – Physiology Departament

PhD Aldo Calliari

External associated researcher
Faculty of Veterinary (Udelar) – Biochemestry Departament (Biophysics Area)

MSc Mariana Bresque

Research assistant; PhD student

Leonardo Santos

Research assitant, PhD student

MSc Laura Colman

Research assistant, PhD student

Pía Garat

Biotech engineer, CEO at EOLO Pharma (Argentina)

Alejandro Rodriguez, BSc

MSc student

Karina Cal, MSc

Lab technician

Md Maria Caggiani

MSc student

MD Adriana Carlomagno, MSc

PhD student
  • DBC1 as modulator of metabolic function. The main focus of our research has been to continue to understand the role of the protein Deleted in Breast Cancer-1 (DBC1), a SIRT1 regulator, in the control of metabolism and metabolic diseases. In order to achieve that, we took four different scientific approaches. A) We continued using the genetic deletion of DBC1 mouse model as an experimental paradigm in metabolism regulation; B) we engaged in studying how DBC1 function is regulated in vivo. C) We decided to generate a loxp/loxp DBC1 mouse model as a tool for tissue-specific knockout of DBC1. D) Based on our previous data that DBC1 regulates the “healthy obesity” phenotype, we began to search for secreted targets of DBC1 that may account for its effects.

  • Novel regulators of metabolism and metabolic diseases: focus on Inflammation. Chronic inflammation has emerged in the past few years as a major player in the development of metabolic diseases, with accumulating evidences showing that both innate and adaptive immune cells are involved in the onset and progression of obesity, type II diabetes and atherosclerosis. During this period, we begun to work with two different proteins in context of chronic inflammation and metabolic diseases: SIRT6 and “TMEM176B.

  • Research and development in anti-obesity drugs. The development of novel compounds for pharmacological treatment of metabolic diseases was a seminal part of our G5 proposal. We associated in close collaboration with Dr. Carlos Batthyany, who together with Dr. Virginia Lopez had already designed several compounds aimed to treat atherosclerosis. Together, we showed that these compounds are effective in vivo for atherosclerosis. In the course of this scientific collaboration, we designed together a novel family of compounds, one of which is showing striking results on prevention of obesity, insulin resistance and non-alcoholic liver steatohepatitis (NASH).

  • 2014-2019 – Young leaders grant. INNOVA – ANII.

  • 2017-2018 – Eolo Pharma: A pharmaceutical company for the development of new compounds for the treatment of metabolic and cardiovascular diseases. CITES-SANCOR. Co-responsible: Carlos Batthyany and Virginia López.

  • 2017-2019 – New role of CD38 in the regulation of acute inflammatory response. R&D scholarship, CSIC. Co-responsible: Paola Contreras

  • 2016-2018 – Agence universitaire de la Francophonie (AUF). Co-responsible: Marcelo Hill (Laboratory of Immunoregulation and Inflammation).

  • 2015-2017 – Role of the DBC1 protein in the physiology of fat tissue during obesity. Clemente Estable Fund. ANII.

  • 2015-2017 – Creation and development of NutraScan – ANII. Alliance Pasteur-Granuy. Co-responsible: Carlos Batthyany.

  • “Treatment methods of conditions related to inflammation using pluripotent anti-inflammatory and metabolic modulators”. Inventors: Batthyany, C., Lopez, G.V., Escande, C., Porcal, W., Dapueto, R., Rodriguez, R., Galliussi, G., and Garat, M.P. 2016. Provisional patent application in the United States; to be assigned // on hold.

  • “Derivatives of trolox and methods of use in the treatment and prevention of conditions related to inflammation”. Inventors: Batthyany, C., Lopez, G.V., Dapueto, R., Escande, C., and Rodriguez, R. 2016. Non-provisional patent application in the United States; to be assigned // on hold.

  • Rodriguez-Duarte J, Dapueto R, Galliussi G, Turell L, Kamaid A, Khoo NKH, Schopfer FJ, Freeman BA, Escande C, Batthyány C, Ferrer-Sueta G, López GV. Electrophilic nitroalkene-tocopherol derivatives: synthesis, physicochemical characterization and evaluation of anti-inflammatory signaling responses.

    Scientific Reports 2018 Aug 24;8(1):12784

  • Prieto-Echague V, Lodh, S,  Colman L, Bobba N, Santos L, Katsanis N, Escande C, Zaghloul N, Badano JL. BBS4 regulates the expression and secretion of FSTL1, a protein that participates in ciliogenesis and the differentiation of 3T3-L1.

    Scientific Reports, 2017. Aug 29;7(1):9765.

  • Matalonga J, Glaria E, Bresque M, Escande C, Carbó JM, Kiefer K, Vicente R, León TE, Beceiro S, Pascual-García M, Serret J, Sanjurjo L, Morón-Ros S, Riera A, Paytubi S, Juarez A, Sotillo F, Lindbom L, Caelles C, Sarrias MR, Sancho J, Castrillo A, Chini EN, Valledor AF. The Nuclear Receptor LXR Limits Bacterial Infection of Host Macrophages through a Mechanism that Impacts Cellular NAD Metabolism.

    Cell Rep. 2017 Jan 31;18(5):1241-1255.

  • Camacho-Pereira J, Tarragó MG, Chini CC, Nin V, Escande C, Warner GM, Puranik  AS, Schoon RA, Reid JM, Galina A, Chini EN. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.

    Cell Metab. 2016 Jun 14;23(6):1127-39

  • Chini CC, Espindola-Netto JM, Mondal G, Guerrico AM, Nin V, Escande C, Sola-Penna M, Zhang JS, Billadeau DD, Chini EN. SIRT1-Activating Compounds (STAC) Negatively Regulate Pancreatic Cancer Cell Growth and Viability Through a SIRT1 Lysosomal-Dependent Pathway.

    Clin Cancer Res. 2016 May 15;22(10):2496-507

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  • Santos L, Escande C, Denicola A. Potential Modulation of Sirtuins by Oxidative Stress.

    Oxid Med Cell Longev. 2016; 2016:9831825. doi: 10.1155/2016/9831825. Review

  • Mathison A*, Escande C*, Calvo E, Seo S, White T, Salmonson A, Faubion WA Jr, Buttar N, Iovanna J, Lomberk G, Chini EN, Urrutia R. Phenotypic Characterization of Mice Carrying Homozygous Deletion of KLF11, a Gene in Which Mutations Cause Human Neonatal and MODY VII Diabetes. Endocrinology.

    2015 Oct;156(10):3581-95. doi: 10.1210/en.2015-1145. Epub 2015 Aug 6. Shared First Authorship

  • Escande C, Nin V, Pirtskhalava T, Chini CC, Tchkonia T, Kirkland JL, Chini EN. Deleted in breast cancer 1 limits adipose tissue fat accumulation and plays a key role in the development of metabolic syndrome phenotype.

    Diabetes. 2015 Jan;64(1):12-22