Metabolic Regulation Lab
We study adipocytes (fat cells) and adipose tissue. In recent years, our focus has been on the molecular control of differentiation, activation and metabolism of brown adipocytes. Our interest in brown adipose tissue biology derives from the striking ability of brown adipocytes to counteract obesity and insulin resistance in experimental animals and the observation that active brown fat is present in many adult humans. Ongoing projects revolve around metabolic regulation and signal transduction. Our aim is to uncover novel regulatory mechanisms through which brown adipose tissue can be exploited therapeutically.
Our aim is to identify novel mechanisms for maintaining/regaining metabolic health through brown adipose tissue.
White and brown adipose tissues play pivotal roles in whole-body energy metabolism. White adipose tissue (WAT) is the largest energy reserve in the body, and white adipocytes secrete hormones (adipokines) affecting various key metabolic organs. Excessive accumulation of WAT causes obesity that predisposes to hypertension, diabetes, cardiovascular disease and certain cancers. Brown adipose tissue (BAT) is specialized in energy dissipation by which the resident brown adipocytes upon activation convert energy-rich substrates to heat by uncoupled respiration (thermogenesis). This uncoupled respiration is induced by cold exposure and is dependent on uncoupling protein 1 (UCP1), which is present exclusively in thermogenic adipocytes. Brown adipocytes, like white adipocytes, secrete adipokines which impact systemic energy metabolism. Brown adipocytes have a striking capacity for clearing circulating lipids and glucose from the bloodstream, and multiple mouse models have demonstrated that increasing BAT activity dramatically improves whole-body insulin sensitivity and glucose homeostasis. Therefore, BAT is considered a target for preventing and treating obesity and diabetes.
Molecular control of brown adipocyte energy metabolism
Brown adipocytes have a very high capacity for substrate oxidation and energy expenditure through uncoupled respiration. Fatty acids are important fuel substrates, but recently we demonstrated a pronounced upregulation of several glucose-dependent metabolic pathways in BAT during exposure to cold (Qin et al., 2015). Therefore, we are now investigating the regulation and importance of oxidation of various substrates, including glucose and fatty acids (Winther et al., 2018). Examples of ongoing projects are transcriptional control of glycolytic gene expression and the involvement of selected metabolic enzymes in energy expenditure by brown adipocytes (Basse et al., 2017; Isidor et al., 2020). We focus on “metabolic breaks”, the inhibition of which may allow oxidation of even more fuel substrates.
Identification of novel signal transduction components regulating brown adipocyte biology
We have carried out chemical compound screens to identify novel regulators of brown adipocyte biology, e.g. thermogenesis and adipokine secretion. The screens revealed targets that were required for brown adipocyte thermogenesis and targets that restricted thermogenesis. We identified numerous novel brown adipocyte regulators and are currently studying a number of these, including signaling proteins and adipokines (Knoll et al., 2017; Markussen et al., 2018). We focus on druggable targets that restrict energy metabolism in our recently established human brown adipocyte cell model (Markussen et al., 2017), as inhibition of such targets may further increase energy dissipation by human adipocytes.
We collaborate with a number of Danish, European and US laboratories.
M. S. Isidor, S. Winther, L. K. Markussen, A. L. Basse, B. Quistorff, J. Nedergaard, B. Emanuelli, J. B. Hansen.*
M. J. Riis-Vestergaard, B. Richelsen, J. M. Bruun, W. Li, J. B. Hansen, S. B. Pedersen.
M. Tozzi, J. B. Hansen, I. Novak.
L. J. Mortensen, M. Lorenzen, N. Jørgensen, A. M. Andersson, J. E. Nielsen, L. I. Petersen, B. Lanske, A. Juul, J. B. Hansen, M. B. Jensen.
S. Winther, M. S. Isidor, A. L. Basse, N. Skjoldborg, A. Cheung, B. Quistorff, J. B. Hansen.*
P. Breining, J. B. Jensen, E. I Gormsen, S. Jakobsen, M. Busk, L. Rolighed, P. Bross, P. Fernandez-Guerra, L. K. Markussen, N. E. Rasmussen, J. B. Hansen, S. B. Pedersen, B. Richelsen, N. Jessen.
Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro.
Diabetes Obes. Metab. 20, 2264-2273. 2018. Link
C. Petersen, M. D. Nielsen, E. S. Andersen, A. L. Basse, M. S. Isidor, L. K. Markussen, B. M. Viuff, I. H. Lambert. J. B. Hansen, S. F. Pedersen.
MCT1 and MCT4 expression and lactate flux activity increase during white and brown adipogenesis and impact adipocyte metabolism.
Sci. Rep. 7, 13101. 2017. Link
A. L. Basse, M. S. Isidor, S. Winther, N. B. Skjoldborg, M. Murholm, E. S. Andersen, S. B. Pedersen, C. Wolfrum, B. Quistorff, J. B. Hansen.*
Regulation of glycolysis in brown adipocytes by HIF-1α.
Sci. Rep. 7, 4052. 2017. Link
PLoS ONE 12(9):e0185624. 2017. Link
M. S. Isidor, S. Winther, A. L. Basse, M. C. H. Petersen, B. Cannon, J. Nedergaard, J. B. Hansen.*
An siRNA-based method for efficient silencing of gene expression in mature brown adipocytes.
Adipocyte 5, 175-185. 2016. Link
P. Hallenborg, E. Fjære, B. Liaset, R. K. Petersen, I. Murano, S. B. Sonne, M. Falkerslev, S. Winther, B. A. H. Jensen, T. Ma, J. B. Hansen, S. Cinti, B. Blagoev, L. Madsen, K. Kristiansen
p53 regulates expression of uncoupling protein 1 through binding and repression of PPARγ coactivator 1α.
Am. J. Physiol. Endocrinol. Metab. 310, E116-128. 2016. Link
U. Liisberg, L. Myrmel, E. Fjære, A. Rønnevik, S. Bjelland, K. Fauske, J. B. Holm, A. L. Basse, J. B. Hansen, B. Liaset, K. Kristiansen, L. Madsen.
The protein source determines the potential of high protein diets to attenuate obesity development in C57BL/6J mice.
Adipocyte 5, 196-211. 2016. Link
A. L. Basse, K. Dixen, R. Yadav, M. P. Tygesen, K. Qvortrup, K. Kristiansen, B. Quistorff, R. Gupta,* J. Wang, J. B. Hansen.*
Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling.
BMC Genomics 16, 215. 2015. Link
Q. Hao, R. Yadav, A. L. Basse, S. Petersen, S. B. Sonne, S. Rasmussen, Q. Zhu, Z. Lu, J. Wang, K. Audouze, R. Gupta, L. Madsen, K. Kristiansen, J. B. Hansen.*
Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism.
Am. J. Physiol. Endocrinol. Metab. 308, E380-E392. 2015. Link
J. Pingel, M. C. H. Petersen, U. Fredberg, S. G. Kjær, B. Quistorff, H. Langberg, J. B. Hansen.*
Inflammatory and metabolic alterations of Kager’s fat pad in chronic Achilles tendinopathy.
PLoS ONE 10:e0127811. 2015. Link
T. L. Vormer, J. B. Hansen, H. te Riele.
The retinoblastoma protein: multi-tasking to suppress tumorigenesis.
Mol. Cell. Oncol. 2:1, e968062. 2015. Link
J. G. Knudsen, M. Murholm, A. L. Carey, R. S. Biensø, A. L. Basse, T. L. Allen, J. Hidalgo, B. A. Kingwell, M. A. Febbraio, J. B. Hansen, H. Pilegaard.
Role of IL-6 in exercise training- and cold-induced UCP1 expression in subcutaneous white adipose tissue.
PLoS ONE 9: e84910. 2014. Link
Y. Jiang, M. Xie, W. Chen, R. Talbot, J. F. Maddox, T. Faraut, C. Wu, D. M. Muzny, Y. Li, W. Zhang, J. A. Stanton, R. Brauning, W. C. Barris, T. Hourlier, B. L. Aken, S. M. Searle, D. L. Adelson, C. Bian, G. R. Cam, Y. Chen, S. Cheng, U. DeSilva, K. Dixen, Y. Dong, G. Fan, I. R. Franklin, S. Fu, P. Fuentes-Utrilla, R. Guan, M. A. Highland, M. E. Holder, G. Huang, A. B. Ingham, S. N. Jhangiani, D. Kalra, C. L. Kovar, S. L. Lee, W. Liu, X. Liu, C. Lu, T. Lv, T. Mathew, S. McWilliam, M. Menzies, S. Pan, D. Robelin, B. Servin, D. Townley, W. Wang, B. Wei, S. N. White, X. Yang, C. Ye, Y. Yue, P. Zeng, Q. Zhou, J. B. Hansen, K. Kristiansen, R. A. Gibbs, P. Flicek, C. C. Warkup, H. E. Jones, V. H. Oddy, F. W. Nicholas, J. C. McEwan, J. W. Kijas, J. Wang, K. C. Worley, A. L. Archibald, N. Cockett, X. Xu, W. Wang, B. P. Dalrymple.
The sheep genome illuminates biology of the rumen and lipid metabolism.
Science 344, 1168-1173. 2014. Link
T. L. Vormer, K. Wojciechowicz, M. Dekker, S. de Vries, A. van der Wal, E. Delzenne-Goette, S. H. Naik, J.-Y. Song, J.-H. Dannenberg, J. B. Hansen,* H. te Riele.*
RB family tumor suppressor activity may not relate to active silencing of E2F target genes.
Cancer Res. 74, 5266-5276. 2014. Link
P. Hallenborg, R. K. Petersen, S. Feddersen, U. Sundekilde, J. B. Hansen, B. Blagoev, L. Madsen, K. Kristiansen.
PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation.
J. Lipid Res. 55, 2491-2500. 2014. Link
K. Dixen, A. L. Basse, M. Murholm, M. S. Isidor, L. H. L. Hansen, M. C. H. Petersen, L. Madsen, N. Petrovic, J. Nedergaard, B. Quistorff, J. B. Hansen.*
ERRγ enhances UCP1 expression and fatty acid oxidation in brown adipocytes.
Obesity 21, 516-524. 2013. Link
M. Murholm, M. S. Isidor, A. L. Basse, S. Winther, C. Sørensen, J. Skovgaard-Petersen, M. M. Nielsen, A. S. Hansen, B. Quistorff, J. B. Hansen.*
Retinoic acid has different effects on UCP1 expression in mouse and human adipocytes.
BMC Cell Biol. 14, 41. 2013. Link
N.-E. Viby, M. S. Isidor, K. B. Buggeskov, S. S. Poulsen, J. B. Hansen, H. Kissow.
Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice.
Endocrinology 154, 4503-4511. 2013. Link
Selected publications before 2013:
R. Hakim-Weber, A. M. Krogsdam, C. Jørgensen, M. Fischer, A. Prokesch, J. G.. Bogner-Strauss, S. R. Bornstein, J. B. Hansen, L. Madsen, K. Kristiansen, Trajanoski Z, Hackl H.
Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation.
BMC Res. Notes 26;4:157. 2011. Link
D. M. Kristensen, M. L. Skalkam, K. Audouze, L. Lesné, C. Desdoits-Lethimonier, H. Frederiksen, S. Brunak, N. E. Skakkebæk, B. Jégou, J. B. Hansen, S. Junker, H. Leffers.
Many putative endocrine disruptors inhibit prostaglandin synthesis.
Environ. Health Perspect. 119:534-541. 2011. Link
L. Madsen, L. M. Pedersen, H. H. Lillefosse, E. Fjære, I. Bronstad, Q. Hao, R. K. Petersen, P. Hallenborg, T. Ma, R. D. Matteis, P. Araujo, J. Mercader, M. L. Bonet, J. B. Hansen, B. Cannon, J. Nedergaard, J. Wang, S. Cinti, P. Voshol, S. O. Døskeland, K. Kristiansen.
UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity.
PLoS ONE 5, e11391. 2010. Link
M. Murholm, K. Dixen, J. B. Hansen.*
Ras signalling regulates differentiation and UCP1 expression in models of brown adipogenesis.
Biochim. Biophys. Acta 1800, 619-627. 2010. Link
Q. Hao, J. B. Hansen, R. K. Petersen, P. Hallenborg, C. Jørgensen, S. Cinti, P. J. Larsen, K. R. Steffensen, H. Wang, S. Collins, J. Wang, J.-Å. Gustafsson, L. Madsen, K. Kristiansen.
ADD1/SREBP1c activates the PGC1α promoter in brown adipocytes.
Biochim. Biophys. Acta 1801, 421-429. 2010. Link
M. Murholm, K. Dixen, K. Qvortrup, L. H. L. Hansen, E.-Z. Amri, L. Madsen, G. Barbatelli, B. Quistorff, J. B. Hansen.*
Dynamic regulation of genes involved in mitochondrial DNA replication and transcription during mouse brown fat cell differentiation and recruitment.
PLoS ONE 4, e8458. 2009. Link
D. Pasini, A. P. Bracken, J. B. Hansen, M. Capillo, K. Helin.
The polycomb group protein Suz12 is required for embryonic stem cell differentiation.
Mol. Cell. Biol. 27, 3769-3779. 2007. Link
K. L. Egerod, B. Holst, P. S. Petersen, J. B. Hansen, J. Mulder, T. Hökfelt, T. W. Schwarz.
GPR39 splice variants versus antisense gene LYPD1: Expression and regulation in gastrointestinal tract, endocrine pancreas, liver and white adipose tissue.
Mol. Endocrinol. 21, 1685-1698. 2007. Link
J. B. Hansen,* K. Kristiansen.*
Pocket proteins control white versus brown fat cell differentiation.
Cell Cycle 5, 341-342. 2006. Link
I. Iankova, R. K. Petersen, J.-S. Annicotte, C. Chavey, J. B. Hansen, I. Kratchmarova, D. Sarruf, M. Benkirane, K. Kristiansen, L. Fajas.
Peroxisome proliferator-activated receptor γ recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis.
Mol. Endocrinol. 20, 1494-1505. 2006. Link
J. B. Hansen,* K. Kristiansen.
Regulatory circuits controlling white versus brown adipocyte differentiation.
Biochem. J. 398, 153-168. 2006. Link
S. Kang, L. Bajnok, K. A. Longo, R. K. Petersen, J. B. Hansen, K. Kristiansen, O. A. MacDougald.
Effects of Wnt signaling on brown adipocyte differentiation and metabolism mediated by PGC-1α.
Mol. Cell. Biol. 25, 1272-1282. 2005. Link
J. B. Hansen, C. Jørgensen, R. K. Petersen, P. Hallenborg, R. De Matteis, H. A. Bøye, N. Petrovic, S. Enerbäck, J. Nedergaard, S. Cinti, H. te Riele, K. Kristiansen.
Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation.
Proc. Natl. Acad. Sci. USA 101, 4112-4117. 2004. Link
J. B. Hansen, H. te Riele, K. Kristiansen.
Novel function of the retinoblastoma protein in fat: regulation of white versus brown adipocyte differentiation.
Cell Cycle 3, 774-778. 2004. Link
J. B. Hansen, R. K. Petersen, C. Jørgensen, K. Kristiansen.
Deregulated MAPK activity prevents adipocyte differentiation of fibroblasts lacking the retinoblastoma protein.
J. Biol. Chem. 277, 26335-26339. 2002. Link
L. Fajas, V. Egler, R. Reiter, J. Hansen, K. Kristiansen, M.-B. Debril, S. Miard, J. Auwerx.
The retinoblastoma-histone deacetylase 3 complex inhibits PPARγ and adipocyte differentiation.
Dev. Cell 3, 903-910. 2002. Link
J. B. Hansen, H. Zhang, T. H. Rasmussen, R. K. Petersen, K. Kristiansen.
Peroxisome proliferator-activated receptor δ (PPARδ)-mediated regulation of preadipocyte proliferation and gene expression is dependent on cAMP signaling.
J. Biol. Chem. 276, 3175-3182. 2001. Link
J. B. Hansen, R. K. Petersen, B. M. Larsen, J. Bartkova, J. Alsner, K. Kristiansen.
Activation of peroxisome proliferator-activated receptor γ bypasses the function of the retinoblastoma protein in adipocyte differentiation.
J. Biol. Chem. 274, 2386-2393. 1999. Link
We contribute to the following courses
Signal Transduction (“Signaltransduktion”)
Molecular Biomedicine BSc program
Cellular Signalling in Health and Disease
Biology, Biochemistry and Biology-Biotechnology MSc programs
Cellular and Integrative Physiology
Biology MSc program
Human Physiology (“Menneskets fysiologi”)
Biology BSc program
Novo Nordisk Foundation
EU FP7 project DIABAT (HEALTH-F2-2011-278373)
Brødrene Hartmanns Fond
Fonden til Lægevidenskabens Fremme
Aase & Ejnar Danielsens Fond
New paper in collaboration with Novo Nordisk out now!
New paper about PKM2 out now in FEBS Letters! Congratulations to Marie and the other co-authors :-)
In addition, a new paper in collaboration with colleagues from Aarhus University Hospital is out - and with a key contribution by Wei!
New paper in collaboration with the Novak lab out now!
New papers in collaboration with the Kristiansen and Blomberg Jensen labs out now!
New paper about the importance of glucose and glycolysis out in AJP-Endo! Congratulations to Sally, Marie and the other co-authors :-)
New paper about GSK3 out in Scientific Reports! Congratulations to Lasse and Sally :-)