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

• DOI: 10.1016/j.cmet.2018.06.020
• Publication Date: 2018-07-20T05:12:24Z
• Authors: Markus Heine; Alexander W. Fischer; Christian Schlein; Caroline Jung; Leon G. Straub; Kristina Gottschling; Nils Mangels; Yucheng Yuan; Stefan K. Nilsson; Gudrun Liebscher; Ou Chen; Renate Schreiber; Rudolf Zechner; Ludger Scheja; Joerg Heeren
• Keywords: Male; Mice, Knockout; 0303 health sciences; Adipose Tissue, White; Lipolysis; Lipoproteins; Adrenergic beta-3 Receptor Agonists; Dioxoles; Lipase; Diet, High-Fat; Receptor, Insulin; Cold Temperature; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Adipocytes, Brown; Adipose Tissue, Brown; Insulin-Secreting Cells; Animals; Insulin; Energy Metabolism; Peptides

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.