Salt Induces Adipogenesis/Lipogenesis and Inflammatory Adipocytokines Secretion in Adipocytes
Salt Induces Adipogenesis/Lipogenesis and Inflammatory Adipocytokines Secretion in Adipocytes
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DOI：
10.3390/ijms20010160
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发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
Kang, Inhae
中科院分区：
文献类型：
--
作者：
Lee, Myoungsook;Sorn, Sungbin Richard;Kang, Inhae
众所周知，高盐摄入与包括高血压在内的心血管疾病有关。然而，关于高盐摄入导致肥胖的机制研究较少。为了评估盐在肥胖患病率中的作用，研究了盐负荷脂肪细胞中脂肪生成/脂肪生成的基因表达和脂肪细胞因子的分泌。高盐剂量依赖性地增加了ppar - γ、C/EBP、SREBP1c、ACC、FAS和aP2等成脂基因的表达，但降低了AMPK等脂肪分解基因的表达，最终导致脂肪堆积。随着SIK-2和Na+/K+- atp酶的激活，盐增加了肾素-血管紧张素-醛固酮系统（RAAS）的代谢物，如ADD1、CYP112和MCR。增加胰岛素依赖性胰岛素受体底物（IRS）信号传导，导致胰岛素抵抗，丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）和Akt-mTOR被激活，而AMPK（Thr(172)）在盐负荷脂肪细胞中被抑制。促炎脂肪因子、TNF、MCP-1、COX-2、IL-17A、IL-6、瘦素和瘦素/脂联素比值（LAR）的表达在盐处理后呈剂量依赖性升高。利用MAPK/ERK抑制剂U0126，我们发现MAPK/ERK、Akt-mTOR信号通路之间的串扰和炎症性脂肪生成可能是盐相关性肥胖的可能机制。高剂量细胞内盐的防御机制是否会激发脂肪细胞分化的信号，或者通过其他途径与周围组织相互作用的可能性将在未来的研究中探索。
It is well known that high salt intake is associated with cardiovascular diseases including hypertension. However, the research on the mechanism of obesity due to high salt intake is rare. To evaluate the roles of salt on obesity prevalence, the gene expression of adipogenesis/lipogenesis and adipocytokines secretion according to adipocyte dysfunction were investigated in salt-loading adipocytes. High salt dose-dependently increased the expression of adipogenic/lipogenic genes, such as PPAR-gamma, C/EBP, SREBP1c, ACC, FAS, and aP2, but decreased the gene of lipolysis like AMPK, ultimately resulting in fat accumulation. With SIK-2 and Na+/K+-ATPase activation, salt increased the metabolites involved in the renin-angiotensin-aldosterone system (RAAS) such as ADD1, CYP112, and MCR. Increasing insulin dependent insulin receptor substrate (IRS)-signaling, resulting in the insulin resistance, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and Akt-mTOR were activated but AMPK(Thr(172)) was depressed in salt-loading adipocytes. The expression of pro-inflammatory adipocytokines, TNF, MCP-1, COX-2, IL-17A, IL-6, leptin, and leptin to adiponectin ratio (LAR) were dose-dependently increased by salt treatment. Using the inhibitors of MAPK/ERK, U0126, we found that the crosstalk among the signaling pathways of MAPK/ERK, Akt-mTOR, and the inflammatory adipogenesis can be the possible mechanism of salt-linked obesity. The possibilities of whether the defense mechanisms against high dose of intracellular salts provoke signaling for adipocytes differentiation or interact with surrounding tissues through other pathways will be explored in future research.