Format

Send to

Choose Destination
Cell Metab. 2018 Oct 2;28(4):644-655.e4. doi: 10.1016/j.cmet.2018.06.020. Epub 2018 Jul 19.

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

Author information

1
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
2
Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
3
Institute of Food, Nutrition and Health, ETH-Zürich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
4
Department of Chemistry, Brown University, 324 Brook Street, Providence, RI 02912, USA.
5
Biocenter, Division of Cell Biology, Medical University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
6
Institute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
7
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: heeren@uke.de.

Abstract

The coordination of the organ-specific responses regulating systemic energy distribution to replenish lipid stores in acutely 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 acute 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.

KEYWORDS:

adaptive thermogenesis; adipose tissue; adipose triglyceride lipase; diabetes mellitus; free fatty acids; insulin; insulin receptor; lipolysis; lipoprotein lipase; obesity

PMID:
30033199
DOI:
10.1016/j.cmet.2018.06.020
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center