Protectin DX ameliorates palmitate-induced hepatic insulin resistance through AMPK/SIRT1-mediated modulation of fetuin-A and SeP expression

被引：18

作者：

Jung, Tae Woo ^{[1
]}

Ahn, Sung Ho ^{[2
]}

Shin, Jong Wook ^{[3
]}

Kim, Hyoung-Chun ^{[4
]}

Park, Eon Sub ^{[2
]}

Abd El-Aty, A. M. ^{[5
,6
]}

Hacimuftuoglu, Ahmet ^{[6
]}

Song, Ki Hak ^{[7
]}

Jeong, Ji Hoon ^{[1
]}

机构：

[1] Chung Ang Univ, Coll Med, Dept Pharmacol, 221 Heuksuk Dong, Seoul 156756, South Korea

[2] Chung Ang Univ, Coll Med, Dept Pathol, Seoul, South Korea

[3] Chung Ang Univ, Coll Med, Dept Internal Med, Seoul, South Korea

[4] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon, South Korea

[5] Cairo Univ, Fac Vet Med, Dept Pharmacol, Giza, Egypt

[6] Ataturk Univ, Med Fac, Dept Med Pharmacol, Erzurum, Turkey

[7] Chungnam Natl Univ, Coll Med, Dept Urol, Daejeon, South Korea

来源：

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | 2019年 / 46卷 / 10期

基金：

新加坡国家研究基金会;

关键词：

AMPK; fetuin-A; hepatocytes; protectin DX; selenoprotein P; SIRT1; ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; SELENOPROTEIN-P; SKELETAL-MUSCLE; AMPK; EXERCISE; LIVER; INFLAMMATION; SENSITIVITY; RESVERATROL;

D O I：

10.1111/1440-1681.13131

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The role as well as the molecular mechanisms of protectin DX (PDX) in the prevention of hepatic insulin resistance, a hallmark of type 2 diabetes, remains unknown. Therefore, the present study was designed to explore the direct impact of PDX on insulin resistance and to investigate the expression of fetuin-A and selenoprotein P (SeP), hepatokines that are involved in insulin signalling, in hepatocytes. Human serum levels of PDX as well as fetuin-A and SeP were determined by high-performance liquid chromatography (HPLC). Human primary hepatocytes were treated with palmitate and PDX. NF-kappa B phosphorylation as well as expression of insulin signalling associated genes and hepatokines were determined by Western blotting analysis. FOXO1 binding levels were measured by quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si) RNA-mediated gene suppression. Serum PDX levels were significantly (P < 0.05) downregulated, whereas serum fetuin-A and SeP levels were increased (P < 0.05) in obese subjects compared with healthy subjects. In in vitro experiments, PDX treatment increased AMP-activated protein kinase (AMPK) phosphorylation and SIRT1 expression and attenuated palmitate-induced fetuin-A and SeP expression and insulin resistance in hepatocytes. AMPK or SIRT1 siRNA mitigated the suppressive effects of PDX on palmitate-induced fetuin-A through NF-kappa B and SeP expression linked to FOXO1 and insulin resistance. Recombinant fetuin-A and SeP reversed the suppressive effects of fetuin-A and SeP expression on palmitate-mediated impairment of insulin signalling. The current finding provides novel insight into the underlying mechanism linking hepatokines to the pathogenesis of hepatic insulin resistance.

引用

页码：898 / 909

页数：12

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