– What is the contribution of adipose tissue dysfunction to the development of systemic dyslipidaemia and cardiovascular disease? Can we influence circulating cholesterol levels by ameliorating adipose tissue health?
Using current cellular and molecular techniques we investigate how our fat cells (adipocytes) contribute to the circulating cholesterol pool, and how lipoprotein-bound cholesterol is taken up and handled by human adipocytes. Our aim is to understand the contribution of the fat tissue to emerging dyslipidaemia and vascular lesions both in humans and atherogenic mice, to better understand the interplay between obesity, increased adipose tissue and the associated increased risk for cardiovascular disease. Ultimately, we want to use our insights from adipose tissue biology to identify novel biomarkers for subjects at heightened cardiovascular risk and characterize new therapeutic targets within the adipose tissue that can be used to lower the risk for disease events.
– Can we develop improved in vitro models for the study of human adipocytes that better mimic the specialized features of this unique cell type?
By combining our insights from adipose tissue biology with recent developments in spheroids culturing our lab has developed a novel adipocyte spheroid model that allows differentiation of human adipocyte progenitors (pre-adipocytes) into mature adipocytes with a largely unilocular cell morphology and larger lipid droplets than any currently available method. The spheroid model is easy to set up and handle and ideally suited for testing lipid dynamics, metabolite fluxes and the influence of drugs on human adipocytes (unpublished data, Hagberg lab).
– What are the vascular pathways governing nutrient uptake from the circulation to the adipocytes?
Timely uptake of nutrients that are meant for storage instead of oxidation is of outmost importance for whole body metabolic balance, but the pathways working within the adipose tissue vascular endothelium to govern nutrient uptake are still poorly understood, as is the balance between enough uptake of lipids to the adipose tissue to protect peripheral organs, and too much uptake, leading to obesity. We aim to decipher the molecular pathways in primary human endothelial cells that govern the uptake of fatty acids, cholesterol and other nutrients to the adipose tissue, and use a combination of in vitro and in vivo models to test their functional relevance for both adipose tissue function and whole-body metabolism in health and obesity.
The Hagberg lab is currently in its third year after joining the Cardiovascular Medicine division at the Department of Medicine Solna at Karolinska Institutet in August 2019. We are also a part of the Centre for Molecular Medicine (CMM) and affiliated to the Strategic Research Programme in Diabetes (SRP Diabetes). Together we have created an inspiring and creative scientific environment characterised by discussion, hard work, collaboration and positivity. I have a long-standing interest in mentorship and believe it is one of the fundamentals of being a group leader. I believe that sharing methodology and knowledge through collaboration can produce science that is beneficiary for all, and only by supporting each other can we bring forward the best science. It is also important that all victories, large and small, should be celebrated and that hard work and perseverance recognized. If you want to know more about me please reach out to me or see my university page at www.ki.se, including a short CV.
My lab offers great science, dedicated mentoring and an inspirational scientific environment! If you have a scholarship or a chance to apply for one please get in touch directly, otherwise check out the funded opportunities below:
The Hagberg lab is a part of the Cardiovascular Medicine division, a well-established larger network of researchers in metabolism, atherosclerosis and cardiovascular inflammation, located on the 8th floor of the brand new BioClinicum Research building at the Karolinska Institutet campus in Solna, Stockholm, Sweden (see map below). The building boasts with newly built labs, open desk and social areas and a stunning view over the university campus. The research division offers an interactive scientific environment focused on both preclinical and clinical cardio-metabolic research with numerous opportunities for collaborative projects and interesting lectures, as well as access to both in-house, Biomedicum and CMM core facilities and seminars.
The Karolinska Institutet university campus (www.ki.se) is situated just outside Stockholm, with good public transport connection to the city centre and close proximity to the buzzling neighbourhood of Rörstrandsgatan and the beautiful Hagaparken. Karolinska Institutet is an entirely medical university, with around 4,700 employees and 2,000 graduate students and its research divided into 22 Departments focusing on all aspects of pre-clinical and clinical medical investigation. This medical focus attracts some of the best researchers to come and lecture at the campus. In addition, the Nobel Assembly at Karolinska Institutet annually selects the Nobel Prize laureates in Physiology and Medicine, and one can attend the prize lectures each year.
18 published papers, H-factor 13, Sum of impact factors 300, Total no. citations 1484 (WoS)
Matúš Soták, Meenu Rohini Rajan, Madison Clark, Christina Biörserud, Ville Wallenius, Carolina E Hagberg, Emma Börgeson. Healthy subcutaneous and omental adipose tissue is associated with high expression of extracellular matrix components.
Int. Journal of Molecular Sciences, 23(1):520 (2022).
Ioannidou A, Fisher RM, Hagberg CE. The multifaceted roles of the adipose tissue vasculature.
Ioannidou A*, Altar S*, Schipper R, Baganha F, Åhlander M, Hornell A, Fisher R, Hagberg CE. Hypertrophied human adipocyte spheroids as in vitro model of weight gain and adipose tissue dysfunction. doi: 10.1113/JP281445. *shared first authors
Journal of Physiology, 600(4):869-883 (2022).
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. Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. *shared first authors
Nature Medicine, 27(11):1941-1953(2021).
Harms MJ, Li Q, Lee S, Zhang C, Kull B, Hallen S, Thorell A, Alexandersson I, Hagberg CE, Peng XR, Mardinoglu A, Kirsty Spalding KL, Boucher J. Mature human adipocytes cultured under permeable membranes maintain identity, function, and can transdifferentiate into brown-like adipocytes.
Cell Reports, 27(1):213-225. 2019
Hagberg CE. Understanding obesity one adipocyte at a time. Science Trends 2018. Link
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. Flow Cytometry of Mouse and Human Adipocytes for the Analysis of Browning and Cellular Heterogeneity.
Cell Reports. 24(10):2746-2756, 2018 #Corresponding author Link
Mehlem A, Palombo I, Wang X, Hagberg CE, Eriksson U, Falkevall A. PGC-1α coordinates mitochondrial respiratory capacity and muscular fatty acid uptake via regulation of VEGF-B.
Diabetes, 65(4):861-73, 2016 Link
Muhl L, Moessinger C, Adzemovic MZ, De Zwart-Dijkstra M, Nilsson I, Zeitelhofer M, Hagberg CE, Huusko J, Falkevall A, Ylä-Herttuala S, Eriksson U. The expres-sion of Vascular Endothelial Growth Factor (VEGF)-B and its receptor (VEGFR1) in the murine heart, lung and kidney.
Cell Tissue Res., 365(1):51-63, 2016 Link
Abreu-Vieira G, Hagberg CE, Spalding KL, Cannon B, Nedergaard J. Adrenergically-stimulated blood flow in brown adipose tissue is not dependent on thermogenesis.
Am J Physiol Endocrinol Metab. 308: E822–E829, 2015 Link
Pirinen E, Canto C, Jo YS, Morato L, Zhang H, Menzies KJ, Williams EG, Mouchiroud L, Moullan N, Hagberg C, Li W, Timmers S, Imhof R, Verbeek J, Pujol A, Van Loon B, Viscomi C, Zeviani M, Schrauwen P, Sauve Aa, Schoonjans K, Auwerx J. Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle.
Cell Metabolism 19;6 1034-41, 2014 Link
Hagberg C*, Mehlem A*, Falkevall A, Muhl L, Eriksson U. Endothelial fatty acid transport: role of vascular endothelial growth factor B.
Physiology 28;2 125-34, 2013 (*equal contribution) Link
Mehlem A, Hagberg CE, Muhl L, Eriksson U, Falkevall A. Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease.
Nature protocols 8;6 1149-54, 2013 Link
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. Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes.
Nature 490;7420 426-30, 2012 (*equal contribution) Link
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. Vascular endothelial growth factor B controls endothelial fatty acid uptake.
Nature 464;7290 917-U136, 2010 Link
Albrecht I, Kopfstein L, Strittmatter K, Schomber T, Falkevall A, Hagberg CE, Lorentz P, Jeltsch M, Alitalo K, Eriksson U, Christofori G, Pietras K. Suppressive Effects of Vascular Endothelial Growth Factor-B on Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Tumorigenesis.
PLOS ONE 5;11 e14109, 2010 Link
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. Vascular Endothelial Growth Factor-B Induces Myocardium-Specific Angiogenesis and Arteriogenesis via Vascular Endothelial Growth Factor Receptor-1-and Neuropilin Receptor-1-Dependent Mechanisms.
Circulation 119;6 845-U134, 2009 Link
Published under maiden name Rosenlew
Diesen C, Saarinen A, Pihko H, Rosenlew C, Cormand B, Dobyns WB, Dieguez J, Valanne L, Joensuu T, Lehesjoki AE. POMGnT1 mutation and phenotypic spectrum in muscle-eye-brain disease.
Journal Of Medical Genetics 41;10, 2004 Link
Published under maiden name Rosenlew.
For more information, research opportunities or collaborations please contact:
Ass. Prof. Carolina Hagberg, PhD
Cardiovascular Medicine, BioClinicum floor 8, J8:20
Akademiska Stråket 1, 171 64 Stockholm