Ginsenoside Rg5 Inhibits Succinate-Associated Lipolysis in Adipose Tissue and Prevents Muscle Insulin Resistance.
Ginsenoside Rg5 Inhibits Succinate-Associated Lipolysis in Adipose Tissue and Prevents Muscle Insulin Resistance.
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DOI：
10.3389/fphar.2017.00043
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发表时间：
2017
影响因子：
5.6
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Xiao N;Yang LL;Yang YL;Liu LW;Li J;Liu B;Liu K;Qi LW;Li P
内质网（ER）应激，炎症和脂解同时发生在脂肪功能障碍，并有助于胰岛素抵抗。本研究旨在探讨Rg 5是否可以改善脂肪功能障碍和预防肌肉胰岛素抵抗。短期高脂饮食（HFD）喂养诱导缺氧与ER应激在脂肪组织中，导致琥珀酸积累由于琥珀酸脱氢酶（SDH）活性逆转。Rg 5处理降低细胞能荷，抑制ER应激，然后阻止琥珀酸在脂肪组织中的积累。琥珀酸盐通过NLRP 3炎性体活化促进IL-1β产生，然后通过损害PDE 3B表达增加cAMP积累，导致脂解增加。人参皂苷Rg 5处理抑制NLRP 3炎性体活化，保留PDE 3B表达，然后减少cAMP积累，有助于抑制脂解。脂肪分解增加了脂肪组织向肌肉的FFA运输。Rg 5可减少二酰甘油（DAG）和神经酰胺的积累，抑制蛋白激酶Cθ转位，预防胰岛素抵抗。总之，缺氧脂肪组织中琥珀酸积累作为一种代谢信号，将ER应激、炎症和cAMP/PKA激活联系起来，导致脂解和胰岛素抵抗。这些发现确立了以前未被认识到的芦荟苷在调节脂质和葡萄糖稳态中的作用，并表明脂肪琥珀酸酯相关的NLRP 3炎性小体激活可能是治疗性靶向，以防止脂解和胰岛素抵抗。
Endoplasmic reticulum (ER) stress, inflammation, and lipolysis occur simultaneously in adipose dysfunction and contribute to insulin resistance. This study was designed to investigate whether ginsenoside Rg5 could ameliorate adipose dysfunction and prevent muscle insulin resistance. Short-term high-fat diet (HFD) feeding induced hypoxia with ER stress in adipose tissue, leading to succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activity. Rg5 treatment reduced cellular energy charge, suppressed ER stress and then prevented succinate accumulation in adipose tissue. Succinate promoted IL-1β production through NLRP3 inflammasome activation and then increased cAMP accumulation by impairing PDE3B expression, leading to increased lipolysis. Ginsenoside Rg5 treatment suppressed NLRP3 inflammasome activation, preserved PDE3B expression and then reduced cAMP accumulation, contributing to inhibition of lipolysis. Adipose lipolysis increased FFAs trafficking from adipose tissue to muscle. Rg5 reduced diacylglycerol (DAG) and ceramides accumulation, inhibited protein kinase Cθ translocation, and prevented insulin resistance in muscle. In conclusion, succinate accumulation in hypoxic adipose tissue acts as a metabolic signaling to link ER stress, inflammation and cAMP/PKA activation, contributing to lipolysis and insulin resistance. These findings establish a previously unrecognized role of ginsenosides in the regulation of lipid and glucose homeostasis and suggest that adipose succinate-associated NLRP3 inflammasome activation might be targeted therapeutically to prevent lipolysis and insulin resistance.