Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity.
Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity.
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DOI：
10.3389/fendo.2013.00001
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发表时间：
2013
影响因子：
5.2
通讯作者：
Takeda Y
中科院分区：
文献类型：
--
作者：
Jetten AM;Kang HS;Takeda Y
视黄酸相关孤儿受体 RORα 和 RORγ 在脂质/葡萄糖稳态和各种免疫功能中发挥调节作用，并与代谢综合征和多种炎症性疾病有关。 RORα 缺陷小鼠可以免受年龄和饮食引起的肥胖、肝脂肪变性和胰岛素抵抗。 RORα缺陷小鼠对肝脂肪变性的抵抗力与调节脂质合成、运输和储存的几种基因的表达减少有关。脂肪组织相关炎症在胰岛素抵抗的发展中起着关键作用，在 RORα 缺陷小鼠中，M1 巨噬细胞浸润减少和许多促炎基因表达减少表明，脂肪组织相关炎症显着减少。 RORγ 缺乏还可以通过与 RORα 缺乏不同的机制来防止饮食引起的胰岛素抵抗。最近的研究表明，ROR 在生物钟机制及其对代谢基因和代谢综合征的调节之间提供了重要的联系。作为配体依赖性转录因子，ROR 可能为肥胖和相关代谢疾病（包括肝脂肪变性、脂肪组织相关炎症和胰岛素抵抗）的治疗提供新的治疗靶点。
Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.