Metabolic Diseases Research (MEDIR)

Our interest is to understand the pathophysiology of prediabetes, type 2 diabetes (T2D) and their comorbidities, and to effectively translate that knowledge into a better diagnosis and treatment of these multi-systemic disorders.

To better understand the pathophysiological mechanisms behind these metabolic diseases, we use an integrative approach looking at classical target tissues for insulin action: liver, muscle, and fat, as well as to other targets (e.g., brain).

In a truly translational approach, we use a wide range of genetic and biochemical approaches both in vitro, ex vivo, in vivo, including studies with human subjects. These studies are expected to lead to the development of novel biomarkers and therapeutic interventions in (pre)diabetes, non-alcoholic fatty liver disease (NAFLD) and to the improvement of health and wellbeing.

To dissect the dynamics of (pre)diabetes and comorbidities, our lab is currently conducting several related and highly integrated projects, for which detailed information is provided below.

Graphical Abstract

GutDerivedExosomes_maria.meneses@nms.un

  • METABOLIC CHRONIC DISEASES STRATIFICATION: A CASE FOR EXOSOMES

Team Members:
Inês Coelho, Rita Machado de Oliveira, Akiko Teshima, Pedro Ribeiro, Pedro Pereira, Paula Macedo

Objective:
We hypothesize that gut-derived exosomes (GDE) can act as mediators of gut-liver communication in T2D and NAFLD pathogenesis and progression. Importantly, blood exosomes cargo and unique surface markers will reflect the metabolic state of multiple organs, thus they hold the potential to be used as a minimally invasive diagnostics tool.
Our ultimate goal is to identify novel biomarkers for T2D and NAFLD stratification towards patient-centered care and precision medicine approaches.

Publications
Ferreira I, Machado de Oliveira R, Carvalho AS, Teshima A, Beck HC, Matthiesen R, Costa-Silva B, Macedo MP. Messages From the Small Intestine Carried by Extracellular Vesicles in Prediabetes: a Proteomic Portrait. bioRxiv 2021.02.19.431856; DOI:10.1101/2021.02.19.431856

Acknowledgments:
SPD; FCT (PTDC/MEC-MET/29314/2017); Programa Gilead Génese

Best_maria.meneses@nms.un

  • BEST - Multifunctional biosensors to integrate in clinical practice and capacitate people with diabetes

    Team members:
    Inês Coelho, Rita Patarrão, Rogério Ribeiro, Rita Andrade, João Raposo, Paula Macedo

    Objetive:
    The goal of this project is to develop a multifunctional sensor to improve the management of diabetes without using complex diagnostic tools.

    Publications
    Pinheiro T, (...) Macedo MP, Águas H, Martins R, Fortunato E. Paper-Based In-Situ Gold Nanoparticle Synthesis for Colorimetric, Non-Enzymatic Glucose Level Determination. Nanomaterials. 2020.14;10(10):2027. doi: 10.3390/nano10102027

    Acknowledgments:
    Portugal2020 (Ref: PT2020/113469)

NAFLD_maria.meneses@nms.un

  • NAFLD/MAFLD: Fatty liver disease

    Team members:
    Maria João Meneses, Inês Sousa-Lima, João Filipe Raposo; Maria Paula Macedo

    Objetives:
    Our current aim is to determine the roles of both PON-1 and ApoJ, two antioxidant proteins produced in the liver, in counteracting the pro-oxidant and pro-inflammatory burden of high-fructose and high-fat diets.

    Publications:
    Meneses MJ, Pina AF, Sousa-Lima I, Patarrao RS, Ribeiro RT, Gardete-Correia L, Duarte R, Boavida JM, Correia I, Andrade R, Medina JL, Raposo JF, Macedo MP, Paraoxonase-1 and Apolipoprotein J as biomarkers in dysmetabolism: a cluster analysis. Diabetologia. 2020;63(SUPPL1):S425-S425.
    Meneses MJ, Silvestre R, Sousa-Lima I, Macedo MP. Paraoxonase-1 as a Regulator of Glucose and Lipid Homeostasis: Impact on the Onset and Progression of Metabolic Disorders. Int J Mol Sci. 2019;20(16). 4049. DOI: 10.3390/ijms20164049

    Acknowledgements:
    SPD-GIFT, FCT (PTDC/BIM-MET/4265/2014; PTDC/BIM-MET/2115/2014, PD/BD/114256/2016), iNOVA4Health (UID/Multi/04462/2013), Marie Skłodowska-Curie Actions H2020 (grant agreements 722619/734719).

 

GeneticStudies_maria.meneses@nms.un

  • From Genetics to Patient Clustering

    Team members:
    Ana Pina, Rita Patarrão, Maria João Meneses, Paula Macedo

    Objetive:
    Our goal is to translate datasets using a system medicine approach into new ways to understand and improve the life and therapeutic decisions that providers and patients make every day.

    Publications:
    Borges DO, Patarrão RS, Ribeiro RT, de Oliveira RM, (...) Macedo MP. Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits. Metabolism. 2021;118. 154735. DOI:10.1016/j.metabol.2021.154735
    Pina ALF, Patarrao RS, Ribeiro RT, (...) Macedo MP. Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia. J Clin Med. 2020;9(8). 2588. DOI: 10.3390/jcm9082588
    Sousa-Lima I, Patarrao RS, Meneses MJ, Pina AF, (...) Macedo MP. Serum levels of the Zonulin family of peptides in individuals from the PREVADIAB2 cohort, a role in metabolic dysfunction. Diabetologia. 2020;63(SUPPL 1):S217-S217

    Acknowledgements:
    SPD, FCT (PTDC/BIM-MET/4265/2014; PTDC/BIM-MET/2115/2014), iNOVA4Health (UID/Multi/04462/2013), Marie Skłodowska-Curie Actions H2020 (grant agreements 722619/734719).
  • BEST – Multifunctional biosensors to integrate in clinical practice and capacitate people with diabetes (2021 - 2023) Projetos de I&D Empresas em Co-Promoção
  • Metabolic chronic diseases stratification: a case for gut-liver axis derived exosomes (09/2018-09/2022) FCT PTDC/MEC-MET/29314/2017
  • Exosomes as Liquid Biopsies for Metabolic Disorders (03/2019-03/2022)- Programa Gilead Génese
  • Coffee protects against NAFLD progression through preservation of intestinal permeability and inhibition of liver fibrosis (2019-2021) Institute for Scientific Information on Coffee, United Kingdom
  • FOIE GRAS – Metabolism and the Gut-liver Axis in Non-Alcoholic Fatty Liver Disease. (2017-2021) Marie Sklodowska-Curie Grant Agreement No. 722619
  • mitoFOIE GRAS: Non-invasive Profiling of Mitochondrial Function in Non-Alcoholic Fatty Liver Disease. (2017-2022) Marie Sklodowska-Curie Grant Agreement No. 734719
  • Hepatic inflammation, insulin clearance and hyperinsulinemia: a triad at the basis of prediabetes. (2016-2019) Fundação para a Ciência e Tecnologia PTDC/BIM-MET/2115/2014.
  • Prognostic and Protective Roles of the Clusterin-PON1 axis Against Obesity Complications (2016-2019) Fundação para a Ciência e Tecnologia PTDC/BIM-MET/4265/2014
  • Insulin Clearance (Dys)Regulation: clarifying the mist. (2013-2016) Fundação para a Ciência e Tecnologia PTDC/DTP-EPI/0207/2012
  • CD26/DPP4 in Fatty Liver Disease progression: inflammation impinges on dysmetabolism. (2013-2015) Fundação para a Ciência e Tecnologia PTDC/BIM-MET/0486/2012
  • Insulin sensitivity is regulated by hepatic glutathione and nitric oxide: a clinical and basic approach. (2005-2010) Fundação para a Ciência e Tecnologia POCI/SAU-OBS/56716/2004 and PPCDT/SAU-OBS/56716/2004
  • Insulin action induced by the postprandial state - from basic science to clinical studies (2009-2013) Fundação para a Ciência e Tecnologia PIC/IC/82956/2007
  • The importance of the hepatic insulin sensitizing substance action in diseases associated with insulin resistance. (2001-2003) Fundação para a Ciência e Tecnologia POCTI/NSE/42397/01
  • Nitric oxide is a major factor in the insulin resistance secondary to the impairment of the hepatic parasympathetic system (1998-2001) Praxis XXI/P/SAU/14009/1998

Borges DO, Patarrão RS, Ribeiro RT, Machado de Oliveira R, Duarte N, Belew GD, Martins M, Andrade R, Costa J, Correia I, Boavida JM, Duarte R, Gardete-Correia L, Medina JL, Raposo JF, Jones JG, Penha-Gonçalves C, Macedo MP. Loss of postprandial insulin clearance control by Insulin-Degrading Enzyme drives dysmetabolism traits. Metabolism. 2021;118:154735. doi: 10.1016/j.metabol.2021.154735.

Coelho I, Duarte N, Barros A, Macedo MP, Penha-Gonçalves C. Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage. Front Immunol. 2021 11:616044. doi: 10.3389/fimmu.2020.616044.

Pina AF, Patarrão RS, Ribeiro RT, Penha-Gonçalves C, Raposo, JF, Gardete-Correia L, Duarte R, Boavida JM, Medina JL, Henriques R, Macedo MP. Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia. Journal of Clinical Medicine 2020, 9(8):2588.

Pina A, Helgadottir S, Mancina RM, ..., Macedo MP, Valenti L, Volpe G, Romeo S. Virtual genetic diagnosis for familial hypercholesterolemia powered by machine learning. European Journal of Preventive Cardiology 2020:2047487319898951. doi: 10.1177/2047487319898951.

Bergman M, Abdul-Ghani M, DeFronzo RA, Manco M, Sesti G, Fiorentino TV, Ceriello A, Rhee M, Phillips LS, Chung S, Cravalho C, Jagannathan R, Monnier L, Colette C, Owens D, Bianchi C, Del Prato S, Monteiro MP, Neves JS, Medina JL, Macedo MP, Ribeiro RT, Raposo JF, Dorcely B, Ibrahim N, Buysschaert M. Review of methods for detecting glycemic disorders. Diabetes Research and Clinical Practice 2020, 165:108233

Borges DO, Meneses MJ, Dias TR, Martins FO, Oliveira PF, Alves MG, Macedo MP. Data on metabolic profile of insulin-degrading enzyme knockout mice. Data Brief. 2019;25:104023. doi:10.1016/j.dib.2019.104023.

Meneses MJ, Silvestre R, Sousa-Lima I, Macedo MP. Paraoxonase-1 as a Regulator of Glucose and Lipid Homeostasis: Impact on the Onset and Progression of Metabolic Disorders. Int J Mol Sci. 2019;20(16):4049. doi: 10.3390/ijms20164049.

Martins F, Delgado T, Viegas J, Gaspar J, O'Doherty R, Scott D, Macedo MP*; Jones J*. Mechanisms by which Thiazolidinediones Protect Against Sucrose-induced Fatty liver and Hyperinsulinemia Br J Pharmacol. 2016 Jan;173(2):267-78.

Natali A, Ribeiro R, Baldi S, Tulipani A, Rossi M, Venturi E, Mari A, Macedo MP, Ferrannini E. Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion. Diabetologia. 2013 May;56(5):1183-91. doi: 10.1007/s00125-013-2836-x

Duarte N, Coelho I, Holovanchuk D, Inês Almeida J, Penha-Gonçalves C, Macedo MP. Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells. Hepatol Commun. 2018 Sep 7;2(9):1080-1094.

João Silva, …, Maria Paula Macedo*, John G. Jones*. Determining Contributions of Exogenous Glucose and Fructose to de novo Fatty Acid and Glycerol Synthesis in Liver and Adipose Tissue. Metabolic Engineering (2019).

Huang H,…, Macedo MP, White M, Jones J, Kim YB. Rho-kinase/AMPK axis regulates hepatic lipogenesis during overnutrition. J Clin Invest. 2018;128(12):5335-5350.

Afonso RA, Gaspar JM, Lamarão I, Lautt WW, Macedo MP. Postprandial insulin action relies on meal composition and hepatic parasympathetics: dependency on glucose and amino acids. J Nutr Biochem. 2016;27:70-8.

Patarrão RS, Lautt WW, Afonso RA, Ribeiro RT, Fernandes AB, Boavida JM, Macedo MP. Postprandial but not fasting insulin resistance is an early identifier of dysmetabolism in overweight subjects. Can J Physiol Pharmacol. 2012;90(7):923-31. doi: 10.1139/y2012-086.

Fernandes AB, Guarino MP, Macedo MP. Understanding the in-vivo relevance of S-nitrosothiols in insulin action. Can J Physiol Pharmacol. 2012;90(7):887-94. doi: 10.1139/y2012-090.
 
 
 

  • 2021 - Portuguese Diabetology Society – Group of Fundamental and Translational Research Prize – Akiko Teshima
  • 2020 - Portuguese Diabetology Society - Charneco da Costa SPD/Sanofi – Rita Machado de Oliveira
  • 2020 - Portuguese Diabetology Society - Nuno Castelo Branco SPD/Lilly – Inês Ferreira
  • 2019 - Prize Program Gilead GÉNESE
  • 2019 - National Diabetology Prize (SPD)
  • 2019 - Portuguese Diabetology Society – Group of Fundamental and Translational Research Prize – Diego Borges
  • 2019 - ortuguese Diabetology Society - Pedro Eurico Lisboa SPD/Lilly – Inês Sousa-Lima
  • 2018 -Portuguese Diabetology Society – Group of Fundamental and Translational Research Prize – Maria João Meneses
  • 2018 - Portuguese Diabetology Society - Nuno Castelo Branco SPD/Lilly
  • 2017 - Best Poster Presentation at I SDF Meeting  (Maria João Meneses)
  • 2017 - Best Poster Presentation at Portuguese Diabetology Society Meeting (Maria João Meneses)
Researcher Inês Coelho wins the Santander/NOVA 2021 Collaborative Research Award

The big winner of the 14th Edition of the Santander Collaborative Research Award/NOVA 2021 is the project “Graphene Smart Bandages for Diabetic Foot Ulcer Monitoring”. The responsible multidisciplinary team is made up of the researcher Inês Coelho, from group MEDIR at CEDOC and  by the researcher João Coelho, from CENIMAT/I3N, from the NOVA School of Science and Technology | NEW FCT.

  • Elvira Fortunato, FCT-NOVA, Caparica, Portugal
  • Wayne Lautt, University of Manitoba, Canada
  • Young Bum-Kim, Beth Israel Deaconess Medical Center, Boston, USA
  • Amalia Gastaldelli, IFC-CNR, Pisa, Italy
  • Piero Portincasa, Università degli Studi di Bari Aldo Moro, Bari, Italy
  • Hans Zischka, Helmholtz Zentrum, Munich, Germany
  • John G Jones, CNC, Coimbra, Portugal
  • Stefano Romeo, Gothenburg University, Gothenburg, Sweden
  • Sonia Najjar, Ohio University, Ohio, USA
  • Norbert Stefan, Tubingen University, Tubingen, Germany
  • Ana Novials, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
  • Bruno Costa-Silva, Fundação Champalimaud, Lisbon, Portugal
  • Carlos Penha-Gonçalves, IGC, Oeiras, Portugal
  • Miguel Castelo Branco, CIBIT, Coimbra, Portugal

Principal Investigator

Maria Paula Macedo
Principal Investigator

Team

João Filipe Raposo
Medical Scientist
Marco Medeiros
Medical Scientist
Rita Patarrão
Assistant Professor
Inês Coelho
Post-Doctoral Fellow
Maria João Meneses
Post-Doctoral Fellow
Rita Machado de Oliveira
Post-Doctoral Fellow
Rogério Ribeiro
Post-Doctoral Fellow
Inês Sousa Lima
Researcher
Ana Rita Andrade
Researcher
Daniela Santos
Investigadora Doutorada
Akiko Teshima
PhD Student
Ana Lúcia Pina
PhD Student
Teresa Ferreira
PhD Student
Pedro Ribeiro
MSc Student
Pedro Pereira
MSc Student