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Carolina Hagberg Group

Targeting lipid handling dynamics in cardiometabolic diseases

About

The Hagberg group studies cellular mechanisms of our major lipid storing cell types – adipocytes, hepatocytes and macrophages – that contribute to the development of obesity-induced metabolic and cardiovascular disorders, with a focus on how lipids are taken up, stored, and used by these cells in health and disease. Our research combines the study of human cells and primary tissue biopsies with the development of novel organotypic tissue models and mechanistic validation in research animals in vivo.

Human subcutaneous adipose tissue piece stained for lipid content (Bodipy, green), nuclei (Hoechst, blue) and vessels (UEA1 lectin, red) and imaged using confocal microscopy, showing the close juxtaposition of the tissue vasculature (in red) with the lipid-storing adipocytes (in green).
The Hagberg lab has pioneered the development of adipose tissue spheroids containing unilocular human white adipocytes, shown here with the lipid droplets stained green with Bodipy. This model can be used for translational studies to better understand how obesity-associated diseases develop and potentially could be prevented.

Research area

Obesity and its associated comorbidities continue to rise worldwide at an alarming rate, with severe socio-economic consequences. A deeper understanding of why overnutrition leads to disease development is urgently needed, so that improved therapeutic and preventive treatments can be developed. Our group studies various aspects of nutrient handling, uptake and storage in humans, with a specific focus on lipid handling by the adipose tissue, macrophage and liver. The overarching objective is to use translational approaches to elucidate pathways that, when disturbed, contribute to the development of cardiometabolic disease, with a particular focus on atherosclerosis and Type 2 Diabetes Mellitus. Our research follows three main lines.

The team of Carolina Hagberg studies lipid handling within our major lipid handling organ, the white adipose tissue. A large part of the work focuses on the crucial role of the microvasculature for adipose tissue lipid uptake and expansion, and uses these insights to, among other, create improved mechanistic in vitro research models such as the human unilocular vascularized adipocyte spheroids, HUVAS (Ioannidou et al, Journal of Physiology, 2022). The team also studies the effect of various nutrients on adipose tissue growth, and in a project led by Professor Rachel Fisher, the role of the perivascular fat found around larger vessels as contributor to the development of cardiovascular disease.

Within the Hagberg team, a study led by Ferdinand Van T Hooft focuses on characterizing novel proteins involved in triglyceride metabolism in liver and the circulation, and the relationships to known disease risk factors and makers of both metabolic and cardiovascular disease.

Lastly, the team of Professor Ewa Ehrenborg focuses their research on the interplay between lipid handling, inflammation and autophagy in relation to cardiovascular disease. Specifically, their interests center around on how lipid handling in macrophages affects inflammation and autophagy during the atherosclerosis process, something that has remained largely unknown. They also aim to identify factors/proteins in the autophagy process that are of relevance for the development of vulnerable plaques and/or progression of atherosclerosis in the vessel wall.

Together, these combined research lines cover a wide range of organs and mechanistic studies into human cardiometabolic pathophysiology, aiming to understand what promotes the emergence of disease during obesity and aging, and providing new therapeutic approaches to reduce disease burden.

Group Leader

Carolina E Hagberg, Group leader, Associate Professor, PhD, Carolina.hagberg@ki.se

I am a Faculty-funded Associate Professor and group leader at Karolinska Institutet in Stockholm, Sweden, working at the Department of Medicine Solna. My group studies the adipose tissue vasculature in health and metabolic disease, combining my previous expertise in vascular biology, nutrient uptake and obesity research. We have a particular interest in understanding how obesity affects adipocyte metabolism and endothelial-adipocyte crosstalk and nutrient transport, and identifying how disruption of these pathways can be used as therapeutic targets to prevent the development of obesity-induced metabolic diseases.

Education, degrees and past experience

2022 Associate professor / Docent in Cell and Molecular Biology

2022 Group Leader at the Department of Medicine Solna (MedS)

2019-2022 Assistant Professor and Team leader at Dept. of MedS

2014-2019 Postdoctoral Fellow in Kirsty Spalding’s lab at ICMC, Medicine Huddinge

2013 Postdoctoral Fellow in the Auwerx/Schoonjans lab at EPFL, Switzerland

2006-2011 PhD student in Ulf Eriksson’s lab, CMB/MBB, Karolinska Institutet

2006 M.Sc. in Biochemistry, University of Helsinki, Finland

2004-2005 Master thesis student in Ralf Pettersson’s Lab, LICR, Karolinska Institutet

2002- 2003 Research internship at INTS/INSERM, Paris, France

2001-2002 Research student at the Folkhälsan Institute of Genetics, Helsinki, Finland

Group members

Rachel Fisher, Professor, rachel.fisher@ki.se

Ferdinand Van T Hooft, Senior Researcher, ferdinand.vant.hooft@ki.se

Ewa Ehrenborg, Team Leader, ewa.ehrenborg@ki.se

Filip Vlavcheski, Postdoc

Ruby Schipper, PhD student, ruby.schipper@ki.se

Alice Maestri, PhD student, alice.maestri@ki.se

Min Cai, PhD student, min.cai@ki.se

Anneli Olsson, Lab manager, anneli.olsson@ki.se

Olivera Werngren, Technician, olivera.werngren@ki.se

Alumni

Shemim Alatar, Anna Ioannidou (now Senior Research Scientist at Sigrid Therapeutics AB), Fabiana Baganha

Funding

Swedish Science Council, Karolinska Institutet Career position and doctoral education grants, European Foundation for the Study of Diabetes (EFSD), Diabetes Wellness Foundation, Åke Wiberg Foundation, Ollie och Elof Ericssons stiftelse, Jeanssons stiftelse and Tore Nilssons Stiftelse.

Prizes & awards

2006 – University of Helsinki prize for Best M.Sc. thesis within Biochemistry

2011 – Swedish Association of Diabetology prize for Best Swedish doctoral thesis in Diabetes

2018 – Faculty funded Assistant Professor position at Karolinska Institutet

2019 – Swedish Research Council Starting Grant

Commissions of trust

2019-2020        Chair of the Karolinska Institutet Junior Faculty; Vice-chair in 2018

2019-2020        Junior Faculty representative at Karolinska Institutet’s Faculty Council

2020-                  Vice chair of the KI Respiratory and Circulatory research Network (KIRCNET)

2020-                  Editorial Board member for the popular science journal Medisinsk Vetenskap

Grant reviewer for French National Research Agency (ANR), UK NC3Rs, Swiss national Science Foundation (SNSF) and Karolinska Institutet KID grants.

Contact and additional information

Lab address:                            BioClinicum J8:20, Visionsgatan 4, 17164 Solna, Sweden
Email:                                        Carolina.hagberg@ki.se
Twitter:                                     @Hagberglab
ORCID:                                       0000-0002-5497-2855
Uni homepage:                       https://staff.ki.se/people/carolina-hagberg
Lab homepage:                       www.Hagberglab.com

Selected publications

Next generation human adipose tissue culture methods. Lauschke VM & Hagberg CE. Current Opinions in Genetics and Development. Accepted manuscript (2023).

 

Hypertrophied human adipocyte spheroids as in vitro model of weight gain and adipose tissue dysfunction. Ioannidou A, Altar S, Schipper R, Baganha F, Åhlander M, Hornell A, Fisher R, Hagberg CE. Journal of Physiology, 600(4):869-883 (2022).

 

The multifaceted roles of the adipose tissue vasculature. Ioannidou A, Fisher RM, Hagberg CE. Obesity Reviews, 23(4):e13403 (2022).

 

Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. Li Q*, Hagberg CE*, Silva Cascales H, Lang S, Hyvönen MT, Salehzadeh F, Chen P, Alexandersson I, Terezaki E, Harms MJ, Kutschke M, Arifen N, Krämer N, Aouadi M, Boucher J, Thorell A, Spalding KL. Nature Medicine, 27(11):1941-1953 (2021). *Shared 1st author

 

Mature human adipocytes cultured under permeable membranes maintain identity, function, and can transdifferentiate into brown-like adipocytes. Harms MJ, Li Q, Lee S, Zhang C, Kull B, Hallen S, Thorell A, Alexandersson I, Hagberg CE, Peng XR, Mardinoglu A, Spalding KL, Boucher J. Cell Reports, 27(1):213-225 (2019)

 

Flow Cytometry of Mouse and Human Adipocytes for the Analysis of Browning and Cellular Heterogeneity. Hagberg CE#, Li Q, Kutschke M, Bhowmick D, Kiss E, Shabalina IG, Harms MJ, Shilkova O, Kozina V, Nedergaard J, Boucher J, Thorell A, Spalding KL#. Cell Reports, 24(10):2746-2756 (2018) #Co-corresponding authors

Adrenergically-stimulated blood flow in brown adipose tissue is not dependent on thermogenesis. Abreu-Vieira G, Hagberg CE, Spalding KL, Cannon B, Nedergaard J. Am J Physiol Endocrinol Metab. 308: E822–E829 (2015)

 

Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. Hagberg CE*, Mehlem A*, Falkevall A, Muhl L, Fam BC, Ortsater H, Scotney P, Nyqvist D, Samen E, Lu L, Stone-Elander S, Proietto J, Andrikopoulos S, Sjoholm A, Nash A, Eriksson U. Nature 490;7420 426-30 (2012) *equal contribution

Vascular endothelial growth factor B controls endothelial fatty acid uptake. Hagberg CE, Falkevall A, Wang X, Larsson E,  Huusko J,  Nilsson I,  van Meeteren LA,  Samen E,  Lu L,  Vanwildemeersch M,  Klar J,  Genove G,  Pietras K,  Stone-Elander S,  Claesson-Welsh L, Yla-Herttuala S,  Lindahl P,  Eriksson U. Nature 464;7290 917-U136 (2010)

Vascular Endothelial Growth Factor-B Induces Myocardium-Specific Angiogenesis and Arteriogenesis via Vascular Endothelial Growth Factor Receptor-1-and Neuropilin Receptor-1-Dependent Mechanisms. Lahteenvuo JE, Lahteenvuo MT, Kivela A, Rosenlew C*, Falkevall A, Klar J, Heikura T, Rissanen TT, Vahakangas E, Korpisalo P, Enholm B, Carmeliet P, Alitalo K, Eriksson U, Yla-Herttuala S. Circulation 119;6 845-U134 (2009) *Maiden name

Full publication list can be found here: https://staff.ki.se/people/carolina-hagberg

About CMM

The Center for Molecular Medicine (CMM) is a foundation instituted by the Stockholm County Council (Region Stockholm). CMM is at the heart of a close partnership with the Karolinska University Hospital and Karolinska Institutet, fueling advancements in biomedical and clinical research.

Contact

Center for Molecular Medicine Foundation, org. nr. 815201-3689

Karolinska University Hospital L8:05

Visionsgatan 18

171 76 Stockholm, Sweden

communication@cmm.se

CMM
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