Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPAR-Dependent AMPK Activation

Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPAR-Dependent AMPK Activation
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DOI:
10.1002/jcp.25715
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发表时间:
2017-08-01
影响因子:
5.6
通讯作者:
Rosa Neto, Jose C.
Rosa Neto, Jose C.
中科院分区:
生物学2区
文献类型:
--
作者:
de Souza, Camila O.;Teixeira, Alexandre A. S.;Rosa Neto, Jose C.

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背景:棕榈油酸被称为脂质因子,通过调节脂肪组织中的 5AMP 激活蛋白激酶 (AMPK) 来增加葡萄糖摄取,并通过激活过氧化物酶体增殖物激活受体 (PPAR) 来增加脂肪分解。然而,在肝脏中,棕榈油酸对葡萄糖代谢的影响以及PPAR的作用仍不清楚。目的:探讨棕榈油酸是否能改善肥胖小鼠的肝脏胰岛素敏感性。方法:C57BL6 和 PPAR 敲除(KO)小鼠用标准饮食(SD)或高脂饮食(HF)喂养 12 周,并在最后 2 周用油酸或棕榈油酸治疗。结果:棕榈油酸促进体内葡萄糖的更快吸收,与更高的胰岛素浓度相关;然而,即使用胰岛素刺激,棕榈油酸也不会调节胰岛素途径(AKT、IRS)。棕榈油酸增加 AMPK 的磷酸化,上调葡萄糖激酶并下调 SREBP-1。对于 AMPK 下游,棕榈油酸增加 FGF-21 的产生并刺激 PPAR 的表达。棕榈油酸治疗不会增加 PPAR KO 小鼠肝脏中的 AMPK 磷酸化、调节葡萄糖激酶或增加 FGF-21。结论:在高脂饮食喂养的小鼠中,补充棕榈油酸通过激活 AMPK 和 FGF-21(依赖于 PPAR)刺激肝脏中葡萄糖的摄取。 J.细胞。生理学。 232:2168-2177,2017 年。(c) 2016 年 Wiley 期刊公司。
Background: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor- (PPAR), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPAR remain unknown. Objective: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice. Methods: C57BL6 and PPAR knockout (KO) mice were fed for 12 weeks with a standard diet (SD) or high-fat diet (HF), and in the last 2 weeks were treated with oleic or palmitoleic acid. Results: Palmitoleic acid promoted a faster uptake of glucose in the body, associated with higher insulin concentration; however, even when stimulated with insulin, palmitoleic acid did not modulate the insulin pathway (AKT, IRS). Palmitoleic acid increased the phosphorylation of AMPK, upregulated glucokinase and downregulated SREBP-1. Regarding AMPK downstream, palmitoleic acid increased the production of FGF-21 and stimulated the expression of PPAR. Palmitoleic acid treatment did not increase AMPK phosphorylation, modulate glucokinase or increase FGF-21 in liver of PPAR KO mice. Conclusions: In mice fed with a high-fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF-21, dependent on PPAR. J. Cell. Physiol. 232: 2168-2177, 2017. (c) 2016 Wiley Periodicals, Inc.