Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway.
Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway.
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DOI：
10.1002/oby.23012
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Zhou YB
中科院分区：
文献类型：
--
作者：
Dai HB;Wang FZ;Kang Y;Sun J;Zhou H;Gao Q;Li ZZ;Qian P;Zhu GQ;Zhou YB
肾上腺髓质素（ADM）具有治疗炎症性疾病的潜力。因此，本研究探讨了ADM对肥胖大鼠内脏白色脂肪组织（vWAT）或脂肪细胞炎症的影响。雄性大鼠喂食高脂饮食12周以诱导肥胖，肥胖大鼠植入渗透微型泵，提供ADM的恒定输注（300 ng/kg/h），并继续喂食高脂饮食4周。与对照组相比，vWAT和脂多糖（LPS）处理的脂肪细胞中ADM和ADM受体的内源性蛋白表达显著增加。ADM显著降低肥胖大鼠vWAT和脂多糖刺激的脂肪细胞中炎症介质TNFα、IL-1β、环氧合酶-2和诱导型一氧化氮合酶的蛋白表达。抑制脂多糖诱导的脂肪细胞炎症信号通路MAPK和NF-κB的激活。ADM受体拮抗剂和cAMP依赖性蛋白激酶（PKA）激活抑制剂可抑制ADM在脂肪细胞中的这些作用。ADM可抑制肥胖大鼠WAT的炎症反应，其机制可能与激活ADM受体和PKA有关。
Adrenomedullin (ADM) possesses therapeutic potential for inflammatory diseases. Consequently, the effects of ADM on inflammation in visceral white adipose tissue (vWAT) of obese rats or in adipocytes were explored in this study. Male rats were fed a high‐fat diet for 12 weeks to induce obesity, and obese rats were implanted with osmotic minipumps providing constant infusion of ADM (300 ng/kg per hour) and continued to be fed a high‐fat diet for 4 weeks. When compared with the control group, endogenous protein expression of ADM and ADM receptors in vWAT and in lipopolysaccharide (LPS)‐treated adipocytes was markedly increased. ADM significantly decreased the protein expression of the inflammatory mediators TNFα, IL‐1β, cyclooxygenase‐2, and inducible nitric oxide synthase in vWAT of obese rats and in adipocytes stimulated by LPS. It also inhibited the activation of the inflammatory signaling pathways MAPK and NF‐κB induced by LPS in adipocytes. These effects of ADM in adipocytes were inhibited by the administration of ADM receptor antagonist and cAMP‐dependent protein kinase (PKA) activation inhibitor. ADM can inhibit inflammation in WAT in obesity, which may be mediated by the activation of ADM receptors and PKA.
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