Apolipoprotein A-IV restrains fat accumulation in skeletal and myocardial muscles by inhibiting lipogenesis and activating PI3K-AKT signalling.

IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Wenqian Zhang, Xiao-Huan Liu, Jin-Ting Zhou, Cheng Cheng, Jing Xu, Jun Yu, Xiaoming Li
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引用次数: 0

Abstract

Background: One of the pathological characteristics of obesity is fat accumulation of skeletal muscles (SKM) and the myocardium, involving mechanisms of insulin resistance and abnormal lipid metabolism. Apolipoprotein A-IV (ApoA-IV) is an essential gene in both glucose and lipid metabolisms.

Materials and methods: Using high-fat diet (HFD) induced obese apoA-IV-knockout mice and subsequent introduction of exogenous recombinant-ApoA-IV protein and adeno-associated virus (AAV)-transformed apoA-IV, we examined lipid metabolism indicators of SKM and the myocardium, which include triglyceride (TG) content, RT-PCR for lipogenic indicators and western blotting for AKT phosphorylation. Similarly, we used high-glucose-fed or palmitate (Pal)-induced C2C12 cells co-cultured with ApoA-IV protein to evaluate glucose uptake, the phosphoinositide 3-kinase (PI3K)-AKT pathway, and lipid metabolisms.

Results: In stable obese animal models, we find ApoA-IV-knockout mice show elevated TG content, enhanced expression of lipogenic enzymes and diminished phosphorylated AKT in SKM and the myocardium, but both stable hepatic expression of AAV-apoA-IV and brief ApoA-IV protein administration suppress lipogenesis and promote AKT phosphorylation. In a myoblast cell line C2C12, ApoA-IV protein suppresses Pal-induced lipid accumulation and lipogenesis but enhances AKT activation and glucose uptake, and the effect is abolished by a PI3K inhibitor.

Conclusion: We find that ApoA-IV reduces fat accumulation by suppressing lipogenesis and improves glucose uptake in SKM and the myocardium by regulating the PI3K-AKT pathway.

载脂蛋白 A-IV 通过抑制脂肪生成和激活 PI3K-AKT 信号,抑制骨骼肌和心肌中的脂肪堆积。
背景:肥胖的病理特征之一是骨骼肌(SKM)和心肌的脂肪堆积,涉及胰岛素抵抗和脂质代谢异常的机制。载脂蛋白 A-IV(ApoA-IV)是葡萄糖和脂质代谢的重要基因:我们使用高脂饮食(HFD)诱导的肥胖载脂蛋白A-IV基因敲除小鼠,随后引入外源重组载脂蛋白A-IV蛋白和腺相关病毒(AAV)转化的载脂蛋白A-IV,检测了SKM和心肌的脂质代谢指标,包括甘油三酯(TG)含量、RT-PCR检测生脂指标和Western印迹检测AKT磷酸化。同样,我们使用高葡萄糖喂养或棕榈酸酯(Pal)诱导的与载脂蛋白A-IV蛋白共培养的C2C12细胞来评估葡萄糖摄取、磷脂肌醇3-激酶(PI3K)-AKT通路和脂质代谢:结果:在稳定的肥胖动物模型中,我们发现 ApoA-IV 基因敲除小鼠表现出 TG 含量升高、脂肪生成酶表达增强以及 SKM 和心肌中 AKT 磷酸化减少,但 AAV-apoA-IV 的肝脏稳定表达和短暂 ApoA-IV 蛋白的给药均可抑制脂肪生成并促进 AKT 磷酸化。在肌母细胞系 C2C12 中,载脂蛋白 ApoA-IV 蛋白抑制了 Pal 诱导的脂质积累和脂肪生成,但增强了 AKT 激活和葡萄糖摄取,且 PI3K 抑制剂可消除这种效应:结论:我们发现 ApoA-IV 通过抑制脂肪生成减少脂肪积累,并通过调节 PI3K-AKT 通路改善 SKM 和心肌的葡萄糖摄取。
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来源期刊
Archives of Physiology and Biochemistry
Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY
CiteScore
6.90
自引率
3.30%
发文量
21
期刊介绍: Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.
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