Adiponectin induced AMP-activated protein kinase impairment mediates insulin resistance in Bama mini-pig fed high-fat and high-sucrose diet.
Adiponectin induced AMP-activated protein kinase impairment mediates insulin resistance in Bama mini-pig fed high-fat and high-sucrose diet.
复制标题
脂联素诱导的 AMP 激活蛋白激酶损伤介导高脂高糖饲料巴马小型猪的胰岛素抵抗
DOI：
10.5713/ajas.17.0006
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Niu M;Xiang L;Liu Y;Zhao Y;Yuan J;Dai X;Chen H
脂肪组织不再被认为是一种惰性的脂质储存器官，而是被认为通过分泌脂肪因子在调节胰岛素效应中发挥积极作用。然而，关于脂肪因子的作用出现了相互矛盾的报道。本研究旨在探讨脂肪因子在肥胖巴马小型猪糖代谢和胰岛素敏感性中的作用。采用高脂高糖饲料饲养巴马小型猪30周，建立肥胖模型。检测血糖、血生化水平，并进行静脉葡萄糖耐量试验。还通过放射免疫测定法检测了脂联素、白细胞介素-6（IL-6）、抵抗素和肿瘤坏死因子α（TNF-α）等脂肪因子以及葡萄糖诱导的胰岛素分泌。用免疫印迹法检测骨骼肌中腺苷酸活化蛋白激酶（AMPK）的磷酸化，AMPK是一种有用的胰岛素抵抗标志物。此外，通过皮尔斯相关分析评估AMPK磷酸化与血浆脂肪因子和胰岛素抵抗的稳态模型评估（HOMA-IR）指数的关联。肥胖猪表现出高血糖、高甘油三酯和胰岛素抵抗。在肥胖猪中，血清和脂肪组织中的脂联素水平显著降低（p<0.05），IL-6量显著增加（p<0.05），证实了来自肥胖小鼠和人的数据。然而，循环TNF-α和TNF-α没有显示出差异，而脂肪组织中TNF-α的值在肥胖猪中显著更高，这也与肥胖人的数据一致，但与啮齿动物模型不一致。此外，骨骼肌AMPK磷酸化与血浆脂联素和HOMA-IR指数有很强的相关性。脂联素降低诱导AMPK损伤介导高脂高糖饮食诱导胰岛素抵抗此外，巴马小型猪有可能成为人类代谢性疾病的理想模型。
Adipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs. An obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor necrosis factor alpha (TNF-α), and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed by Pearce’s correlation analysis. Obese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and TNF-α showed no difference, while the values of TNF-α in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained. AMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable model for human metabolic diseases.