首页> 外文期刊>The Journal of Nutritional Biochemistry >The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase alpha 1 subunit
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The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase alpha 1 subunit

机译:甜菜碱对功能异常的脂肪组织和N6-甲基腺苷mRNA甲基化的有益作用需要AMP激活的蛋白激酶α1亚基

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The current study was conducted to determine whether betaine could improve fatty acid oxidation, mitochondrial function and N6-methyladenosine (m(6)A) mRNA methylation in adipose tissue in high-fat-induced mice and how AMP-activated protein kinase al subunit (AMPK alpha 1) was involved. AMPKal knockout mice and wild-type mice were fed either a low-fat diet, high-fat diet or high-fat diet supplemented with betaine in the drinking water for 8 weeks. Our results showed that mitochondrial genes (PGC1 alpha) and beta-oxidation-related genes (CPT1a) at protein level were increased in wild-type mice supplemented with betaine when compared with those in mice with high-fat diet. Betaine also decreased FTO expression and improved m(6)A methylation in adipose tissue of wild-type mice with high-fat diet. However, betaine failed to exert the abovementioned effects in AMPK alpha 1 knockout mice. In adipocytes isolated from mice with high-fat diet, betaine treatment increased lipolysis and lipid oxidation. Moreover, betaine decreased FTO expression and increased m(6)A methylation. However, while AMPK alpha 1 was knockdown, no remarkable changes in adipocytes were observed under betaine treatment. Our results indicated that betaine supplementation rectified mRNA hypomethylation and high FTO expression induced by high-fat diet, which may contribute to its beneficial effects on impaired adipose tissue function. Our results suggested that the AMPK alpha 1 subunit is required for the beneficial effects of betaine on dysfunctional adipose tissue and m(6)A methylation. These results may provide the foundation for a mechanism that links m(6)A methylation status in RNA, AMPK alpha 1 phosphorylation and dysfunctional adipose tissue induced by high-fat diet. (C) 2015 Elsevier Inc. All rights reserved.
机译:当前的研究是为了确定甜菜碱是否可以改善高脂诱导的小鼠脂肪组织中的脂肪酸氧化,线粒体功能和N6-甲基腺苷(m(6)A)mRNA甲基化以及AMP激活的蛋白激酶a1亚基如何(涉及AMPK alpha 1)。在饮用水中给AMPKal基因敲除小鼠和野生型小鼠喂养低脂饮食,高脂饮食或补充有甜菜碱的高脂饮食8周。我们的结果表明,与高脂饮食的小鼠相比,补充甜菜碱的野生型小鼠的蛋白质水平线粒体基因(PGC1 alpha)和与β氧化相关的基因(CPT1a)含量增加。甜菜碱还可以降低高脂饮食野生型小鼠脂肪组织中FTO的表达并改善m(6)A甲基化。但是,甜菜碱未能在AMPK alpha 1基因敲除小鼠中发挥上述作用。在从高脂饮食小鼠中分离出的脂肪细胞中,甜菜碱处理可增加脂解作用和脂质氧化作用。此外,甜菜碱降低FTO表达并增加m(6)A甲基化。但是,虽然AMPK alpha 1被敲低,但在甜菜碱处理下,未观察到脂肪细胞的显着变化。我们的结果表明,补充甜菜碱可纠正高脂饮食诱导的mRNA低甲基化和高FTO表达,这可能有助于其对受损的脂肪组织功能的有益作用。我们的结果表明,甜菜碱对功能失调的脂肪组织和m(6)A甲基化的有益作用需要AMPK alpha 1亚基。这些结果可能提供了一种机制,可以将高脂肪饮食诱导的RNA中的m(6)A甲基化状态,AMPKα1磷酸化和功能异常的脂肪组织联系起来。 (C)2015 Elsevier Inc.保留所有权利。

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