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Influence of glucocorticoids on human brown adipose tissue and cold induced thermogenesis

Applicant Betz Matthias
Number 167823
Funding scheme Ambizione
Research institution
Department Klinische Forschung Universitätsspital Basel
Abteilung Endokrinologie, Diabetologie und Metabolismus Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Clinical Endocrinology
Start/End 01.05.2017 - 30.06.2021
Approved amount 614'856.00
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All Disciplines (3)

Discipline
Clinical Endocrinology
Endocrinology
Physiology : other topics

Keywords (10)

temperature regulation; glucocorticoid excess; insulin resistance; glucocorticoid; Cushing's syndrome; brown adipose tissue; obesity; energy expenditure; diabetes; thermogenesis

Lay Summary (German)

Lead
Das braune Fettgewebe (brown adipose tissue, BAT) ist ein auf Wärmeproduktion spezialisiertes Gewebe, das durch einen Kurzschlussmechanismus in den Mitochondrien chemische Energie aus Fett in Wärme umwandeln kann. Der Einfluss einer Behandlung mit Cortisonpräparaten (Glucocorticoiden) auf dieses Gewebe ist beim Menschen bislang noch nicht systematisch untersucht worden.
Lay summary

Inhalt und Ziele des Forschungsprojekts

In Experimenten an Tieren und braunen Fettzellen ist festgestellt worden, dass Glucocorticoide die Wärmeproduktion im braunen Fettgewebe senken und insbesondere die Neubildung von braunem Fettgewebe aus dem weissen Fettgewebe hemmen. Das Forschungsvorhaben ist untergliedert in drei Teilprojekte. Im ersten Projekt werden die Auswirkungen einer einwöchigen Gabe eines Glucocorticoids im Vergleich zu einem Scheinmedikament (Placebo) auf das BAT bei gesunden Freiwilligen untersucht. Hierzu wird der Energieverbrauch der Personen bei Wärme und milder Kälte und die Blutzuckeraufnahme in das BAT gemessen. Im zweiten Teilprojekt werden diese Untersuchungen bei Patienten durchgeführt, bei denen eine Behandlung mit Glucocorticoiden über einen Zeitraum von mindestens sechs Wochen geplant ist. Das dritte Teilprojekt untersucht Gewebeproben von Patienten, die wegen eines Glucocorticoid-produzierenden gutartigen Tumors operiert wurden.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Die Bedeutung des BAT beim erwachsenen Menschen ist erst in den letzten Jahren besser verstanden worden: Aktives BAT wirkt sich günstig auf den Fett- und Blutzuckerstoffwechsel aus und könnte dabei helfen, Übergewicht zu vermeiden. Es ist daher wichtig, den Einfluss von häufig genutzten Medikamenten wie Glucocorticoiden auf dieses Gewebe zu kennen.

Direct link to Lay Summary Last update: 27.03.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Resting Energy Expenditure and Cold Induced Thermogenesis in Patients with Overt Hyperthyroidism.
Maushart Claudia Irene, Senn Jaël Rut, Loeliger Rahel Catherina, Siegenthaler Judith, Bur Fabienne, Fischer Jonas Gabriel William, Betz Matthias Johannes (2021), Resting Energy Expenditure and Cold Induced Thermogenesis in Patients with Overt Hyperthyroidism., in The Journal of clinical endocrinology and metabolism, na.
Free Thyroxine Levels are Associated with Cold Induced Thermogenesis in Healthy Euthyroid Individuals
Maushart Claudia Irene, Senn Jaël Rut, Loeliger Rahel Catherina, Kraenzlin Marius E., Müller Julian, Becker Anton S., Balaz Miroslav, Wolfrum Christian, Burger Irene A., Betz Matthias Johannes (2021), Free Thyroxine Levels are Associated with Cold Induced Thermogenesis in Healthy Euthyroid Individuals, in Frontiers in Endocrinology, 12, 666595.
Relation of diet-induced thermogenesis to brown adipose tissue activity in healthy men
Loeliger Rahel Catherina, Maushart Claudia Irene, Gashi Gani, Senn Jaël Rut, Felder Martina, Becker Anton S., Müller Julian, Balaz Miroslav, Wolfrum Christian, Burger Irene A., Betz Matthias Johannes (2021), Relation of diet-induced thermogenesis to brown adipose tissue activity in healthy men, in American Journal of Physiology-Endocrinology and Metabolism, 320(1), E93-E101.
Low-dose 18F-FDG TOF-PET/MR for accurate quantification of brown adipose tissue in healthy volunteers
ter Voert Edwin E. G. W., Svirydenka Hanna, Müller Julian, Becker Anton S., Balaz Miroslav, Efthymiou Vissarion, Maushart Claudia Irene, Gashi Gani, Wolfrum Christian, Betz Matthias J., Burger Irene A. (2020), Low-dose 18F-FDG TOF-PET/MR for accurate quantification of brown adipose tissue in healthy volunteers, in EJNMMI Research, 10(1), 5-5.
Comparison of [18F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity
Fischer Jonas Gabriel William, Maushart Claudia Irene, Becker Anton S., Müller Julian, Madoerin Philipp, Chirindel Alin, Wild Damian, ter Voert Edwin E. G. W., Bieri Oliver, Burger Irene, Betz Matthias Johannes (2020), Comparison of [18F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity, in EJNMMI Research, 10(1), 85-85.
Cold Exposure Distinctively Modulates Parathyroid and Thyroid Hormones in Cold-Acclimatized and Non-Acclimatized Humans
Kovaničová Zuzana, Kurdiová Tímea, Baláž Miroslav, Štefanička Patrik, Varga Lukáš, Kulterer Oana C, Betz Matthias J, Haug Alexander R, Burger Irene A, Kiefer Florian W, Wolfrum Christian, Ukropcová Barbara, Ukropec Jozef (2020), Cold Exposure Distinctively Modulates Parathyroid and Thyroid Hormones in Cold-Acclimatized and Non-Acclimatized Humans, in Endocrinology, 161(7), 1.
Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation
Balaz Miroslav, Becker Anton S., Balazova Lucia, Straub Leon, Müller Julian, Gashi Gani, Maushart Claudia Irene, Sun Wenfei, Dong Hua, Moser Caroline, Horvath Carla, Efthymiou Vissarion, Rachamin Yael, Modica Salvatore, Zellweger Caroline, Bacanovic Sara, Stefanicka Patrik, Varga Lukas, Ukropcova Barbara, Profant Milan, Opitz Lennart, Amri Ez-Zoubir, Akula Murali K., Bergo Martin, et al. (2019), Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation, in Cell Metabolism, 29(4), 901-916.e8.
Resolution of Hypothyroidism Restores Cold-Induced Thermogenesis in Humans
Maushart Claudia Irene, Loeliger Rahel, Gashi Gani, Christ-Crain Mirjam, Betz Matthias Johannes (2019), Resolution of Hypothyroidism Restores Cold-Induced Thermogenesis in Humans, in Thyroid, 29(4), 493-501.
Outdoor Temperature Influences Cold Induced Thermogenesis in Humans
Senn Jaël R., Maushart Claudia I., Gashi Gani, Michel Regina, Lalive d’Epinay Murielle, Vogt Roland, Becker Anton S., Müller Julian, Baláz Miroslav, Wolfrum Christian, Burger Irene A., Betz Matthias J. (2018), Outdoor Temperature Influences Cold Induced Thermogenesis in Humans, in Frontiers in Physiology, 9, 1.
Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease
Betz Matthias J., Enerbäck Sven (2017), Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease, in Nature Reviews Endocrinology, 14(2), 77-87.

Collaboration

Group / person Country
Types of collaboration
ETH Zürich Department of Biosystems Science and Engineering l, Prof. Carsten Borgwardt Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
MRI Physics Research Group, University Hospital of Basel, Prof. Bieri Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Lab of Claudia Cavelti, Department of Biomedicine, University Hospital Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
ETH Zürich, Prof. Dr. Nicola Zamboni Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
NNF Center for Basic Metabolic Research, Prof. Camilla Schéele Denmark (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Endocrine Research Lab, University Hospital Munich, Prof. Dr. Beuschlein Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Lab of Prof. Sven Enerbäck, Sahlgrenska Academy, University of Gothenburg Sweden (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Department of Nuclear Medicine, University Hospital Zurich, PD Dr. Irene Burger Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
ETHZ Zurich, Prof. Dr. Christian Wolfrum Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Dept. of Radiology and Nuclear Medicine, Prof. Damian Wild, University Hospital Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
20th European Congress of Endocrinology Poster Cold induced thermogenesis is influenced by seasonal changes in outdoor temperature. 19.05.2018 Barcelona, Spain Maushart Claudia; Betz Matthias; Gashi Gani;
20th European Congress of Endocrinology Poster Magnetic Resonance Imaging of Human Supraclavicular Brown Adipose Tissue. 19.05.2018 Barcelona, Spain Gashi Gani; Betz Matthias; Maushart Claudia;


Associated projects

Number Title Start Funding scheme
201065 Therapeutic Targeting of the cAMP and cGMP Pathway to Increase Brown Adipose Tissue Activity in Humans 01.11.2021 Project funding (Div. I-III)

Abstract

Brown adipose tissue (BAT) is unique in its capability to convert chemical energy directly into heat. It is crucial to the survival of newborn infants and small mammals exposed to cold. The recent discovery of active BAT in human adults revealed exciting new aspects of human energy metabolism. Active BAT increases energy expenditure and can thereby counteract obesity and insulin resistance. BAT could thus serve as a potential therapeutic target to treat obesity and its associated diseases. Glucocorticoids (GCs) are frequently used in clinical therapy to suppress immune response in auto-immune, inflammatory and pulmonary diseases. However, their long-term use is associated with weight gain and insulin resistance. While the effects on GCs on glucose metabolism are quite well studied, data on energy expenditure in humans is scarce. Moreover, in vitro and animal data point towards an inhibiting effect of GCs on BAT function and development. This has hitherto not been investigated in humans.The aim of this project is to study both the acute and long-term effect of GCs on human BAT and cold induced thermogenesis (CIT) using a translational and multidisciplinary approach employing state-of-the-art imaging and molecular analysis. The project will be divided into three sub-projects: 1) The first projects aims to investigate the acute effect of one week of high-dose glucocorticoids on human BAT function and cold induced thermogenesis in an investigator-blinded, cross-over trial in healthy volunteers. Techniques used will comprise measurement of cold induced thermogenesis (CIT) by indirect calorimetry, functional and anatomic MRI, as well as molecular analysis of muscle and adipose tissue biopsies.2) The second project is designed as an observational study in patients requiring high-dose glucocorticoids for six weeks. It will comprise measurement of CIT, measurement of glucose uptake into cold stimulated BAT by 18F-FDG-PET/CT and measurement of novel biomarkers of BAT function.3) The third project will investigate the prevalence of retroperitoneal BAT in patients undergoing surgery for benign adrenal tumors and its relation to glucocorticoid secretion. We will analyze the tissue using real-time-PCR, Western-blotting and immunohistochemistry for classical markers of BAT and for recently described transcription factors that have been shown in rodents to be influenced by GC exposure.Together, these projects will allow us to develop a comprehensive overview of the consequences of GC excess on BAT and CIT.
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