Using cellular and molecular techniques I want to understand how our fat cells (adipocytes) adapt to excess nutrients and identify the changes that cause adipocytes to become dysfunctional during obesity.
My goal is to pinpoint novel mechanisms contributing to obesity-induced metabolic disorders in order to find improved therapeutic targets to halt and treat these diseases. Specifically I am interested in how obesity impacts adipocyte energy metabolism and how vascular endovthelial cells regulate nutrient storage in the adipose tissue both in the physiological and obese context. My interest and insights into the field steam from a PhD in vascular biology and postdoc in human adipose biology performed at Karolinska Institutet, Sweden, in combination with a postdoc in cellular energy metabolism and mitochondrial function at EPFL in Switzerland. My lab combines unique molecular techniques with the study human clinical adipose tissue biopsies, and uses cell culture and mice to validate our findings.
Primary isolated mature human adipocytes stained with green LCA-lectin to visualize the cell membrane and blue Hoechst to visualized the nuclei, imaged using confcal microscopy.
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. Recently it was demonstrated that human loss-of-function mutations in the gene coding for a key lipogenic protein localized to the adipose tissue vascular wall greatly impaired lipid uptake and predisposed patients to cardio-metabolic disease (Lotta et al., Nature Genetic, 2017). These results show that further unbiased studies of vascular nutrient transport pathways in the adipose tissue are needed to understand how and when different types of nutrients are taken up for storage, and hence the fundamental pathways governing how adipose tissue expands and obesity develops.
In vitro differentiated human adipocytes stained for lipid droplets (green, Bodipy), cell membrane (red, LCA-lectin) and nuclei (blue, Hoechst).
Impact of obesity-induced endothelial hypertrophy on adipose tissue nutrient transport and vascular function?
Compensatory hypertrophy develops to make up for cellular or functional loss, and is a major pathogenic mechanism in a multitude of tissues, including heart cardiomyocytes, kidney podocytes or pancreatic beta-cells. It involves enlargement of the cellular mass that can have great consequences on both function and metabolism of the cells, and whose initiating cues and pathways vary between cell types and are poorly understood. Endothelial hypertrophy has been studied within the cardiology field but has not been studied for the adipose tissue vascular bed, which is in charge of all nutrient exchange to and from the tissue in the fed and fasted stated, respectively. The project aims to study the impact of endothelial hypertrophy on tissue function and if inhibiting it can have positive effects on whole-body metabolic health.
Human subcutaneous adipose tissue piece stained for lipid content (Bodipy, green), nuclei (Hoechst, blue) and vessels (UEA1 lectin, red)and imaged using confocal microscopy.
The Hagberg lab is currently in its first year and starting up as a part of the Cardiovascular Medicine unit at Karolinska Institutet. My aim is to create an inspiring and creative scientific environment characterised by free-thinking, 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 and collaborating 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 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:
Master thesis student. Looking for 1-2 motivated and enthusiastic students for a 3-12 months project studying the metabolic adaptation of adipocytes and endothelial cells to obesity and weight gain. Previous laboratory experience and good communication skills a plus. Courses in cellular metabolism or biochemistry also helpful. A small scholarship can be provided.
For further information please send your CV together with reference information to Carolina.firstname.lastname@example.org
The Hagberg lab is a part of the Cardiovascular Medicine unit at the Department of Medicine Solna, and located in 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 Cardiovascular Medicine unit offers an interactive scientific environment focused on both preclinical and clinical cardio-metabolic research with numerous opportunities for collaborative projects and interesting lectures. The unit is also a part of the Centre for Molecular Medicine (CMM) with many core facilities and organized seminars.
Photography Ulf Sirborn.
The Karolinska Institutet university campus (www.ki.se) is situated just outside the Stockholm city centre, 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 studnets 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 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.
13 published papers, H-factor 11, Sum of impact factors 180, Total no. citations 857 (WoS)
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. Manuscript accepted in Cell Rep. 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 Rep. 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 oportunities or collaborations please contact:
Ass.prof. Carolina Hagberg, PhD
Cardiovascular Medicine unit, Bioclinicul floor 8
Solnavägen 30, 171 64 Stockholm