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Jan Boren

Professor

Jan Boren
Professor , Head of Department
Jan.Boren@wlab.gu.se
+46 31-342 2949

Postal Address: Box 428, 40530 Göteborg
Visiting Address: Medicinaregatan 3, plan 5 , 41390 Göteborg


Institute of Medicine (More Information)
Box 428
405 30 Göteborg
www.medicine.gu.se
medicin@gu.se
Fax: +46 31823925
Visiting Address: Medicinaregatan 3, plan 5 , 413 90 Göteborg

About Jan Boren

Professor and Chair of Department of Molecular and Clinical Medicine

Jan Borén is Professor and Chair of Department of Molecular and Clinical Medicine at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, and physician at the Department of Clinical Chemistry at the Sahlgrenska University Hospital. He obtained his medical degree at the University of Gothenburg, where he also completed his PhD.

His main long-term interest lipid metabolism and he has focused to understand the underlying mechanisms that lead to, and consequences of lipid accumulation in the liver, arterial wall and heart, with the goal of translating this knowledge into effective treatment. His research program is translational and involves both in vitro and in vivo studies including pathophysiological studies and mouse models, and kinetic studies in carefully phenotyped human volunteers.

He is a member of Royal Society of Arts and Sciences in Gothenburg, and has awarded numerous honours including the Göran Gustafsson’s Prize in Medicine from the Royal Academy of Sciences, Dr. Eric K Fernström Foundation’s Research Award, and Irvine H. Page Atherosclerosis Research Award. He serves as Vice-President of the European Atherosclerosis Society (EAS), and is Editorial Board Member for Arteriosclerosis, Thrombosis, and Vascular Biology, Section editor for BBA – Molecular and Cell Biology of Lipids and co-Editor of Atherosclerosis.

Education & Degrees

  • 1999 Associate Professor (docent) in Molecular Medicine, University of Gothenburg
  • 1994–1998 Research Fellow and Staff Research Investigator, Gladstone Institute of Cardiovascular Disease, Univ. of California San Francisco, San Francisco, CA
  • 1992 PhD, Department of Medical Biochemistry, University of Gothenburg, Sweden
  • 1988 MD, University of Gothenburg, Gothenburg, Sweden

Distinctions, Scholarships and Awards (selected)

  • 2013– Member, Royal Society of Arts and Sciences in Gothenburg
  • 2004 Göran Gustafsson’s Prize in Medicine from the Royal Academy of Sciences
  • 2004 The Mejlan (Meilahti) Award, Biomedicum, Helsinki, Finland
  • 2000 Dr. Eric K Fernström Foundation’s Prize to Young Swedish Scientists
  • 1999–2001 Junior Grant for “Young Promising Investigators” from Swedish Foundation for Strategic Research (SSF)
  • 1997 Irvine H. Page Atherosclerosis Research Awards for Young Investigators,
  • American Heart Association, 70th Scientific Sessions
  • 1994–97 Howard Hughes Medical Institute Postdoctoral Fellowship for Physicians
  • 1994 Fulbright Award for Advanced Studies in Biochemistry

National and International Assignments of Importance (selected)

  • 2017– Vice-President European Atherosclerosis Society
  • 2007– Chairman, Dept. of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg
  • 2006–2012 Director, Strategic Research Center, Sahlgrenska Center for Cardiovascular and Metabolic Research
  • 2005–2017 Treasurer European Atherosclerosis Society
  • 2000–2006 Director, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg

Main Research

CAUSES AND CONSEQUENCES OF CARDIOMETABOLIC DISEASES
Obesity is a well-known risk factor for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Importantly, obesity is not only associated with lipid accumulation in adipose tissue, but also in non-adipose tissues. This ectopic lipid accumulation is now recognized as an important link between obesity and its comorbidities. It is not clear how ectopic lipid accumulation induces cellular dysfunction, but elucidation of the underlying mechanisms is important to identify novel therapeutic targets. The overall aim for our research group is to understand the underlying mechanisms that lead to, and consequences of, lipid accumulation in the liver, arterial wall and heart, with the goal of translating this knowledge into effective diagnosis, prevention and treatment.

Fatty liver is linked to increased CVD morbidity and mortality
Non-alcoholic fatty liver disease (NAFLD) is defined as hepatic fat accumulation that exceeds 5% of liver weight in individuals who do not consume significant amounts of alcohol. In the past 2–3 decades, we have seen a marked increase in NAFLD, and it is now the most common cause of chronic liver disease in western countries. Approximately 25–30% of adults have NAFLD, and its prevalence increases to 70–90% among adults with obesity or type 2 diabetes.

Although NAFLD may progress to severe liver diseases the most common cause of death in patients with NAFLD is CVD. This is – at least partly – explained by the fact that NAFLD associates with an atherogenic dyslipidemia characterized by increased triglycerides, low high-density lipoproteins (HDL), accumulation of small dense low-density lipoproteins (LDL) and postprandial hyperlipidemia (i.e., increased blood lipids following a meal). Our laboratory has made significant contributions to the current understanding of this harmful dyslipidemia.

Specifically, we have shown that: (1) the different components of the dyslipidemia are metabolically linked; (2) a central pathophysiological feature is hepatic fat accumulation, which induces hepatic overproduction of large triglyceride-rich very low-density lipoprotein (VLDL1); (3) the impaired removal of triglyceride-rich lipoproteins (TRLs) induces postprandial hyperlipidemia and accumulation of atherogenic TRL remnants; (4) the impaired removal of TRLs associates with increased plasma concentration of apoC-III (Figure 1); and (5) insulin fails to suppress VLDL1 secretion in subjects with high liver fat.

Retention of atherogenic lipoproteins and their role in atherogenesis
Atherogenesis is initiated by subendothelial accumulation of atherogenic lipoproteins. Lipoprotein retention only occurs in specific vascular areas and is mediated by artery wall proteoglycans in the innermost layer of the artery (the arterial intima). We identified the sequence in apolipoprotein B (apoB, the major protein component of low density lipoproteins [LDL]) that binds to the artery wall proteoglycans and showed a causal relationship between lipoprotein–proteoglycan interactions and development of atherosclerosis.

These studies experimentally proved that LDL is causatively linked to atherogenesis and that subendothelial retention of atherogenic apoB-containing lipoproteins is an early key pathogenic event in atherosclerosis. We have further shown that intimal hyperplasia functions as a sink for atherogenic lipoproteins and thus accelerates atherogenesis. Retained and aggregated lipoproteins provoke a series of local biological responses that eventually include maladaptive cellular responses in the arterial wall that accelerate lipoprotein retention and other features of plaque development.

Lipid accumulation in the heart causes cardiac dysfunction
We and others have shown that lipid accumulation in the heart associates with cardiac dysfunction and heart failure in humans. Cardiac fat accumulation has also been proposed to contribute to the high mortality following myocardial infarction in subjects with type 2 diabetes. We recently identified a novel mechanism for lipid accumulation in ischemic hearts and showed that this lipid accumulation resulted in impaired heart function.

Specifically, we showed that (1) the very low density lipoprotein receptor (VLDLr) is highly upregulated in hypoxic cardiomyocytes and in human and mouse ischemic hearts causing a detrimental lipid accumulation; and that (2) VLDLr deficiency in mice results in increased survival and reduced infarct area following a myocardial infarction. These findings show that cardiac lipid accumulation results in increased vulnerability to ischemia, and emphasize the importance of identifying the lipids and molecular mechanisms that induce these destructive responses.

Group Members

Staff scientist

  • Liliana Håversen, PhD
  • Linda Andersson, PhD
  • Malin Lindbom, PhD
  • Mikael Rutberg, PhD

Postdoctoral Fellow

  • Martina Klevstig, PhD

PhD Student

  • Elias Björnson
  • Matias Ekstrand

Research Associate

  • Eva Hedman Sabler
  • Maria Heyden
  • Kristina Skålen
  • Elin Stenfeldt

Guest Professor

  • Kevin Williams, MD, PhD

Key Publications

Mardinoglu A, Björnson E, Zhang C, Klevstig M, Ståhlman M, Adiels M, Hakkarainen A, Lundblom N, Kilicarslan M, Hallström BM, Lundbom J, Barrett PHR, Watts GF, Serlie M, Uhlén M, Nielsen J, Smith U, Marschall HU, Taskinen MR, Borén J.
Personalized genome-scale modeling identifies NAD+ and glutathione metabolism as a target for treatment of NAFLD.
Mol Syst Biol. 13(3):916. (2017)

Lee S, Zhang C, Kilicarslan M, Piening BD, Bjornson E, Hallström BM, Groen Ak, Ferrannini E, Laakso M, Snyder M, Blüher M, Uhlén M, Nielsen J, Smith U, Serlie M, Borén J, Mardinoglu A.
Integrated network analysis reveals an association between plasma mannose levels and insulin resistance and secretion.
Cell Metabol. 24(1):172-84 (2016)

Borén J, Watts GF, Adiels M, Söderlund S, Chan D, Hakkarainen A, Lundbom N, Matikainen N, Kahri J, Vergès B, Barrett PH, Taskinen MR.
Kinetic and related determinants of plasma triglyceride concentration in abdominal obesity: a multicenter tracer kinetic study.
Arterioscler Thromb Vasc Biol. 35(10):2218-24. (2015)

Levin MC, Jirholt P, Wramstedt A, Johansson ME, Gustafsson Trajkovska M, Lundberg A, Ståhlman M, Fogelstrand P, Brisslert M, Fogelstrand L, Yan ZQ, Hansson G, Björkbacka H, Olofsson SO and Borén J.
Rip2 deficiency leads to increased atherosclerosis despite decreased inflammation.
Circ Res. 109:1210-8. (2011)

Perman J, Boström P. Lindbom M, Ståhlman M, Hägg D, Lindskog H, Mattsson Hultén L, Jeppsson A, Petursson P, Herlitz J, Olivecrona G, Strickland DK, Ekroos K, Olofsson S-O, Borén J.
The VLDL Receptor Promotes Lipotoxicity and Increases Mortality in Mice Following an Acute Myocardial Infarction.
J Clin Invest. 121:2625-40. (2011)

Boström P, Rutberg M, Andersson L, Perman J, Lindberg U, Johansson BR, Fernades-Rodriges J, Ericsson J, Nilsson T, Borén J, Olofsson S-O.
SNARE proteins mediates the fusion between cytosolic lipid droplets with implications for insulin sensitivity.
Nat Cell Biol. 9:1286–93 (2007)

Gustafsson M, Levin M, Skålén K, Perman J, Fridén V, Jirholt P, Olofsson, SO, Fazio S, Linton MF, Semenkovich CF, Olivecrona G, Borén J.
Retention of LDL in Atherosclerotic Lesions of the Mouse: Evidence for a Role of Lipoprotein Lipase.
Circ Res. 101:777–83. (2007)

Skålen K, Gustafsson M, Rydberg EK, Hulten L.M, Wiklund O, Innerarity TL, Borén J.
Subendothelial retention of atherogenic lipoproteins in early atherosclerosis.
Nature. 417:750-754 (2002)

Borén J, Olin K, Lee I, Chait A, Wight T.N, Innerarity TL.
Identification of the principal proteoglycan binding site in LDL: A single point mutation in apolipoprotein B100 severely affects proteoglycan interaction without affecting LDL receptor binding.
J Clin Invest. 101:2658–2664. (1998)

Borén J, Lee I, Zhu W, Arnold K, Taylor S, Innerarity TL.
Identification of the LDL Receptor Binding Site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective apo-B100.
J Clin Invest. 101:1084–1093. (1998)

Latest publications

Dietary Fructose and the Metabolic Syndrome
M. R. Taskinen, C. J. Packard, Jan Borén
Nutrients, Journal article 2019
Journal article

Protein kinase MST3 modulates lipid homeostasis in hepatocytes and correlates with nonalcoholic steatohepatitis in humans.
Emmelie Cansby, Nagaraj M. Kulkarni, Elin Magnusson, Yeshwant Kurhe, Manoj Amrutkar et al.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Journal article 2019
Journal article

The Potential Use of Metabolic Cofactors in Treatment of NAFLD
A. Mardinoglu, D. Ural, M. Zeybel, H. H. Yuksel, M. Uhlen et al.
Nutrients, Journal article 2019
Journal article

Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
P. Saliba-Gustafsson, M. Pedrelli, K. Gertow, O. Werngren, V. Janas et al.
Journal of Internal Medicine, Journal article 2019
Journal article

Targeting filamin A reduces macrophage activity and atherosclerosis.
Sashidar Bandaru, Chandu Ala, Reza Salimi, Murali K Akula, Matias Ekstrand et al.
Circulation, Journal article 2019
Journal article

Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia
Martin Adiels, M. R. Taskinen, Elias Björnson, Linda Andersson, N. Matikainen et al.
Diabetes, obesity and metabolism, Journal article 2019
Journal article

Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics
Elias Björnson, C. J. Packard, Martin Adiels, L. Andersson, N. Matikainen et al.
Journal of Internal Medicine, Journal article 2019
Journal article

Showing 241 - 245 of 245

2004

Dermal absorption of camphor, menthol, and methyl salicylate in humans
D. Martin, J. Valdez, Jan Borén, M. Mayersohn
J Clin Pharmacol, Journal article 2004
Journal article

2003

2002

Expression of scavenger receptor class B type I in gallbladder columnar epithelium.
Magnus S.C. Johnson, Per-Arne Svensson, Jan Borén, Håkan Billig, Lena M S Carlsson et al.
Journal of gastroenterology and hepatology, Journal article 2002
Journal article

Showing 241 - 245 of 245

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Utskriftsdatum: 2019-11-17