<br>对脂肪传入反射的脂肪分解反应减少，与肥胖中肾上腺素受体-cAMP-PKA-激素敏感脂肪酶途径的激活受损有关。,Scientific Reports

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对脂肪传入反射的脂肪分解反应减少，与肥胖中肾上腺素受体-cAMP-PKA-激素敏感脂肪酶途径的激活受损有关。
Scientific Reports ( IF 3.8 ) Pub Date : 2016-10-03 , DOI: 10.1038/srep34374
Lei Ding ₁ , Feng Zhang ₁ , Ming-Xia Zhao ₁ , Xing-Sheng Ren ₁ , Qi Chen ₂ , Yue-Hua Li ₂ , Yu-Ming Kang ₃ , Guo-Qing Zhu ₁

Affiliation

白色脂肪组织 (WAT) 的化学刺激会引起脂肪传入反射 (AAR) 和交感神经激活。本研究旨在探讨 AAR 对脂肪分解的影响以及肥胖中 AAR 增强导致脂肪分解反应减弱的机制。大鼠因高脂肪饮食12周而导致肥胖。 AAR是通过将辣椒素注射到腹股沟WAT中或电刺激附睾WAT传入神经来诱导的。 AAR 引起交感神经激活，在肥胖大鼠中这种激活增强。 AAR 增加 cAMP 水平和 PKA 活性，促进激素敏感脂肪酶 (HSL) 和周脂质磷酸化，并增加 WAT 中的脂肪分解，这些作用在肥胖大鼠中减弱。肥胖大鼠脂肪细胞中 PKA 活性、cAMP、perilipin 和 β-肾上腺素受体水平降低，而 HSL 上调。在原代脂肪细胞中，异丙肾上腺素增加 cAMP 水平和 PKA 活性，促进 HSL 和周脂蛋白磷酸化，并增加脂肪分解，但在肥胖大鼠中这种作用减弱。 cAMP 类似物 dbcAMP 可以防止肥胖大鼠脂肪细胞中异丙肾上腺素的减弱作用。结果表明，肥胖者对 AAR 增强的脂解反应降低归因于 β-肾上腺素受体 -cAMP-PKA-HSL 通路激活受损。脂肪细胞中 cAMP 水平的增加可以纠正肥胖症中减弱的脂肪分解作用。

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Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity.

Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity.

更新日期：2016-10-05

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