Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src.
Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src.
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DOI：
10.1371/journal.pone.0139638
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Okajima F
中科院分区：
文献类型：
--
作者：
Uchiyama T;Tomono S;Sato K;Nakamura T;Kurabayashi M;Okajima F
代谢综合征的特点是内脏肥胖、胰岛素抵抗、高甘油三酯（TG）和低高密度脂蛋白胆固醇水平、高血压和糖尿病，所有这些往往会导致心脑血管疾病。然而，目前尚不清楚为什么内脏肥胖而不是皮下肥胖会导致胰岛素抵抗和其他病理情况。脂蛋白脂肪酶 (LPL) 催化血浆脂蛋白中的 TG 水解。在本研究中，我们研究了血管紧张素 II (AngII) 对 TG 代谢的影响是否是通过影响 LPL 表达来介导的。脂肪组织分为内脏脂肪组织（VAT）和皮下脂肪组织（SAT）进行比较。 AngII 加速 SAT 中 LPL 的表达，但相反，抑制其在 VAT 中的表达。在 SAT 和 VAT 中，AngII 通过相同的 1 型受体发出信号。在 SAT 中，AngII 通过 c-Src 和 p38 MAPK 信号传导增加 LPL 表达。然而，在 VAT 中，AngII 通过 Gq 类 G 蛋白以及随后的磷脂酶 C β4 (PLCβ4)、蛋白激酶 C β1、核因子 κB 和诱导型一氧化氮合酶信号通路降低 LPL 表达。 PLCβ4小干扰RNA实验表明，PLCβ4表达对于AngII诱导的VAT中LPL降低很重要，其中PLCβ4表达在晚上增加，在夜间下降。有趣的是，VAT中PLCβ4的表达随着禁食而降低，而AngII在禁食状态下并没有降低VAT中LPL的表达。总之，AngII通过PLCβ4降低LPL表达，PLCβ4的表达受VAT喂养的调节，而AngII增加SAT中LPL的表达。 AngII 对 LPL 表达以及 VAT 和 SAT 中 TG 代谢的不同影响可能部分解释了它们对代谢综合征发展的不同贡献。
Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG)- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes—all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL) catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII) on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the Gq class of G proteins and the subsequent phospholipase C β4 (PLCβ4), protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome.