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Lipolysis Triggers a Systemic Insulin Response Essential for Efficient Energy Replenishment of Activated Brown Adipose Tissue in Mice

36 Pages Posted: 10 Apr 2018 Sneak Peek Status: Published

See all articles by Markus Heine

Markus Heine

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Alexander W. Fischer

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Christian Schlein

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Caroline Jung

University Medical Center Hamburg-Eppendorf - Department for Diagnostic and Interventional Radiology and Nuclear Medicine

Leon G. Straub

ETH Zurich - Institute of Food, Nutrition and Health

Kristina Gottschling

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Nils Mangels

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Yucheng Yuan

Brown University - Department of Chemistry

Stefan K. Nilsson

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Ou Chen

Brown University - Department of Chemistry

Renate Schreiber

University of Graz - Institute of Molecular Biosciences

Rudolf Zechner

University of Graz - Institute of Molecular Biosciences

Ludger Scheja

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Joerg Heeren

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

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Abstract

The coordination of the organ-specific responses regulating systemic energy distribution to replenish lipid stores in activated brown adipose tissue (BAT) remains elusive. Here, we show that short-term cold-exposure or acute β3-adrenergic receptor (β3AR) stimulation results in secretion of the anabolic hormone insulin. This process is diminished in adipocyte-specific Atgl-/- mice indicating that lipolysis in white adipose tissue (WAT) promotes insulin secretion. Inhibition of pancreatic β cells abolished uptake of lipids delivered by triglyceride-rich lipoproteins into activated BAT. Both increased lipid uptake into BAT and whole body energy expenditure in response to β3AR stimulation were blunted in mice treated with the insulin receptor antagonist S961 or lacking the insulin receptor in brown adipocytes. In conclusion, we introduce the concept that cold and β3AR stimulation trigger a systemic response involving WAT, β cells and BAT, which is essential for insulin-dependent fuel uptake and adaptive thermogenesis.

Suggested Citation

Heine, Markus and Fischer, Alexander W. and Schlein, Christian and Jung, Caroline and Straub, Leon G. and Gottschling, Kristina and Mangels, Nils and Yuan, Yucheng and Nilsson, Stefan K. and Chen, Ou and Schreiber, Renate and Zechner, Rudolf and Scheja, Ludger and Heeren, Joerg, Lipolysis Triggers a Systemic Insulin Response Essential for Efficient Energy Replenishment of Activated Brown Adipose Tissue in Mice (2018). Available at SSRN: https://ssrn.com/abstract=3155888 or http://dx.doi.org/10.2139/ssrn.3155888
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Markus Heine

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Martinistraße 52
Hamburg, 20251
Germany

Alexander W. Fischer

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Martinistraße 52
Hamburg, 20251
Germany

Christian Schlein

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Martinistraße 52
Hamburg, 20251
Germany

Caroline Jung

University Medical Center Hamburg-Eppendorf - Department for Diagnostic and Interventional Radiology and Nuclear Medicine

Martinistr 52
Building O22
Hamburg, 20246
Germany

Leon G. Straub

ETH Zurich - Institute of Food, Nutrition and Health

Schmelzbergstrasse 7
Zürich, 8092
Switzerland

Kristina Gottschling

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Martinistraße 52
Hamburg, 20251
Germany

Nils Mangels

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Martinistraße 52
Hamburg, 20251
Germany

Yucheng Yuan

Brown University - Department of Chemistry

324 Brook Street
Box H
Providence, RI 02912
United States

Stefan K. Nilsson

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Martinistraße 52
Hamburg, 20251
Germany

Ou Chen

Brown University - Department of Chemistry

324 Brook Street
Box H
Providence, RI 02912
United States

Renate Schreiber

University of Graz - Institute of Molecular Biosciences

Humboldtstraße 50/EG
Graz, 8010
Austria

Rudolf Zechner

University of Graz - Institute of Molecular Biosciences

Humboldtstraße 50/EG
Graz, 8010
Austria

Ludger Scheja

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology

Martinistraße 52
Hamburg, 20251
Germany

Joerg Heeren (Contact Author)

University Medical Center Hamburg-Eppendorf - Department of Biochemistry and Molecular Cell Biology ( email )

Martinistraße 52
Hamburg, 20251
Germany

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