Hurtado Del Pozo, CarmenFriedline, Randall H.Noh, Hye LimKim, Jason KSchmidt, Ann Marie.2022-08-232022-08-232019-07-162019-08-09<p>Cell Rep. 2019 Jul 16;28(3):773-791.e7. doi: 10.1016/j.celrep.2019.06.061. <a href="https://doi.org/10.1016/j.celrep.2019.06.061">Link to article on publisher's site</a></p>2211-1247 (Electronic)10.1016/j.celrep.2019.06.06131315054https://hdl.handle.net/20.500.14038/41123<p>Full author list omitted for brevity. For the full list of authors, see article.</p>Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this receptor in energy metabolism. Here, we demonstrate that mice bearing global- or adipocyte-specific deletion of Ager, the gene encoding RAGE, display superior metabolic recovery after fasting, a cold challenge, or high-fat feeding. The RAGE-dependent mechanisms were traced to suppression of protein kinase A (PKA)-mediated phosphorylation of its key targets, hormone-sensitive lipase and p38 mitogen-activated protein kinase, upon beta-adrenergic receptor stimulation-processes that dampen the expression and activity of uncoupling protein 1 (UCP1) and thermogenic programs. This work identifies the innate role of RAGE as a key node in the immunometabolic networks that control responses to nutrient supply and cold challenges, and it unveils opportunities to harness energy expenditure in environmental and metabolic stress.en-USCopyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/RAGEadaptive thermogenesisadipocyteadipose tissueadvanced glycation end productscold toleranceobesityprotein kinase Areceptor for advanced glycation end productssignal transductionAmino Acids, Peptides, and ProteinsBiochemical Phenomena, Metabolism, and NutritionCellular and Molecular PhysiologyEnzymes and CoenzymesGenetic PhenomenaNutritional and Metabolic DiseasesPathological Conditions, Signs and SymptomsTissuesJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4927&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/391115087830oapubs/3911