Article ; Online: A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis.
2019 Volume 28, Issue 3, Page(s) 773–791.e7
Abstract: 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) ...
| Abstract | 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 β-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. |
|---|---|
| MeSH term(s) | Adipocytes/enzymology ; Adipocytes/metabolism ; Adipose Tissue/enzymology ; Adipose Tissue/metabolism ; Animals ; Cell Line ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Energy Metabolism ; Fasting/metabolism ; Fasting/physiology ; Humans ; Lipolysis/genetics ; Lipolysis/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/genetics ; Obesity/metabolism ; Phosphorylation ; Receptor for Advanced Glycation End Products/antagonists & inhibitors ; Receptor for Advanced Glycation End Products/metabolism ; Signal Transduction/genetics ; Signal Transduction/physiology ; Thermogenesis/genetics ; Transplantation, Homologous ; Uncoupling Protein 1/genetics ; Uncoupling Protein 1/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism |
| Chemical Substances | Receptor for Advanced Glycation End Products ; Ucp1 protein, mouse ; Uncoupling Protein 1 ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) |
| Language | English |
| Publishing date | 2019-08-06 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2649101-1 |
| ISSN | 2211-1247 ; 2211-1247 |
| ISSN (online) | 2211-1247 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2019.06.061 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.