Research group Carolina Hagberg
We study the 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.
Lipid handling in health and cardiometabolic disease
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.
- Fabiana Baganha, PhD, Postdoctoral researcher.
- Min Cai, PhD student.
- Rachel Fisher, PhD, Professor.
- Ferdinand Van T Hooft, MD, PhD, Researcher.
- Anneli Olsson Laboratory Assistant.
- Ruby Schipper PhD Student.
Team Ewa Ehrenborg, MD, PhD, Professor.
- The Swedish Research Council.
- The Swedish Heart Lung foundation.
- Jeanssons stiftelser.
- Åke Wibers stiftelse.
- Tore Nilssons stiftelse.
- Karolinska Institutet.
Hypertrophied human adipocyte spheroids as in vitro model of weight gain and adipose tissue dysfunction.
Ioannidou A, Alatar S, Schipper R, Baganha F, Åhlander M, Hornell A, Fisher RM, Hagberg CE
J Physiol 2022 02;600(4):869-883
The multifaceted roles of the adipose tissue vasculature.
Ioannidou A, Fisher RM, Hagberg CE
Obes Rev 2022 04;23(4):e13403
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, Knibbe C, Boucher J, Thorell A, Spalding KL
Nat Med 2021 11;27(11):1941-1953
Cardiac expression of the microsomal triglyceride transport protein protects the heart function during ischemia.
Klevstig M, Arif M, Mannila M, Svedlund S, Mardani I, Ståhlman M, Andersson L, Lindbom M, Miljanovic A, Franco-Cereceda A, Eriksson P, Jeppsson A, Gan LM, Levin M, Mardinoglu A, Ehrenborg E, Borén J
J Mol Cell Cardiol 2019 12;137():1-8
Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy.
Saliba-Gustafsson P, Pedrelli M, Gertow K, Werngren O, Janas V, Pourteymour S, Baldassarre D, Tremoli E, Veglia F, Rauramaa R, Smit AJ, Giral P, Kurl S, Pirro M, de Faire U, Humphries SE, Hamsten A, , Gonçalves I, Orho-Melander M, Franco-Cereceda A, Borén J, Eriksson P, Magné J, Parini P, Ehrenborg E
J Intern Med 2019 12;286(6):660-675
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 Rep 2018 09;24(10):2746-2756.e5
Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease.
Gertow J, Ng CZ, Mamede Branca RM, Werngren O, Du L, Kjellqvist S, Hemmingsson P, Bruchfeld A, MacLaughlin H, Eriksson P, Axelsson J, Fisher RM
Kidney Int Rep 2017 Nov;2(6):1208-1218
Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle.
Pirinen E, Cantó 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
Cell Metab 2014 Jun;19(6):1034-41
Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes.
Hagberg CE, Mehlem A, Falkevall A, Muhl L, Fam BC, Ortsäter H, Scotney P, Nyqvist D, Samén E, Lu L, Stone-Elander S, Proietto J, Andrikopoulos S, Sjöholm A, Nash A, Eriksson U
Nature 2012 Oct;490(7420):426-30
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, Ylä-Herttuala S, Lindahl P, Eriksson U
Nature 2010 Apr;464(7290):917-21