Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism and Diabetes
Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Enzymes and Coenzymes | Genetic Phenomena | Nutritional and Metabolic Diseases | Pathological Conditions, Signs and Symptoms | Tissues
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.
RAGE, adaptive thermogenesis, adipocyte, adipose tissue, advanced glycation end products, cold tolerance, obesity, protein kinase A, receptor for advanced glycation end products, signal transduction
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Copyright 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/).
DOI of Published Version
Cell Rep. 2019 Jul 16;28(3):773-791.e7. doi: 10.1016/j.celrep.2019.06.061. Link to article on publisher's site
Hurtado Del Pozo, Carmen; Friedline, Randall H.; Noh, Hye Lim; Kim, Jason K.; and Schmidt, Ann Marie., "A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis" (2019). Open Access Articles. 3911.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Amino Acids, Peptides, and Proteins Commons, Biochemical Phenomena, Metabolism, and Nutrition Commons, Cellular and Molecular Physiology Commons, Enzymes and Coenzymes Commons, Genetic Phenomena Commons, Nutritional and Metabolic Diseases Commons, Pathological Conditions, Signs and Symptoms Commons, Tissues Commons