A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis
A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis
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DOI：
10.1016/j.celrep.2019.06.061
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发表时间：
2019-07-16
期刊：
影响因子：
8.8
通讯作者：
Schmidt, Ann Marie
中科院分区：
文献类型：
--
作者：
del Pozo, Carmen Hurtado;Ruiz, Henry H.;Schmidt, Ann Marie
能量平衡的精细调节可以防止营养缺乏，但在营养过剩时会导致代谢功能障碍。在人类和小鼠脂肪组织中，晚期糖基化终末产物（AGEs）受体配体的积累伴随着肥胖，暗示该受体参与能量代谢。在这里，我们证明，小鼠轴承全球或脂肪细胞特异性缺失的Ager，基因编码的脂肪酸，显示上级代谢恢复后禁食，寒冷的挑战，或高脂肪饲料。RAGE依赖性机制可追溯到抑制蛋白激酶A（PKA）介导的磷酸化的关键目标，酶敏感脂肪酶和p38丝裂原活化蛋白激酶，β-肾上腺素能受体刺激过程，抑制解偶联蛋白1（UCP 1）和产热程序的表达和活性。这项工作确定了Rheumatoid作为免疫代谢网络中控制对营养供应和寒冷挑战的反应的关键节点的先天作用，并揭示了利用环境和代谢应激中的能量消耗的机会。
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.