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反式脂肪酸加剧合成代谢类固醇引起的肌肉、胰腺和脂肪组织代谢紊乱和差异基因表达。

Trans-fatty acids aggravate anabolic steroid-induced metabolic disturbances and differential gene expression in muscle, pancreas and adipose tissue.

机构信息

Department of Animal Biology, Federal University of Viçosa, 36570-000, Minas Gerais, Brazil.

Institute of Biomedical Sciences, Department of Structural Biology, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil.

出版信息

Life Sci. 2019 Sep 1;232:116603. doi: 10.1016/j.lfs.2019.116603. Epub 2019 Jun 27.

DOI:10.1016/j.lfs.2019.116603
PMID:31254587
Abstract

AIMS

Although anabolic steroids (AS) and trans-fatty acids overload exerts systemic toxicity and are independent risk factors for metabolic and cardiovascular disorders, their interaction remains poorly understood. Thus, we investigated the impact of a diet rich in trans-fatty acids (HFD) combined with AS on glycemic control, lipid profile, adipose tissue, skeletal muscle and pancreas microstructure and expression of genes involved in energy metabolism.

MAIN METHODS

Forty-eight C57BL/6 mice were randomized into 6 groups treated for 12 weeks with a standard diet (SD) or a diet rich in C18:1 trans-fatty isomers (HFD), alone or combined with 10 or 20 mg/kg testosterone cypionate (AS).

KEY FINDINGS

Our results indicated that AS improved glycemic control, upregulated gene expression of Glut-4 and CPT-1 in skeletal muscle, FAS, ACC and UCP-1 in adipose tissue. AS also reduced total and LDL cholesterol in mice fed a SD. When combined with the HFD, AS was unable to induce microstructural adaptations in adipose tissue, pancreatic islets and β-cells, but potentiated GCK and Glut-2 (pancreas) and Glut-4 and CPT-1 (skeletal muscle) upregulation. HFD plus AS also downregulated FAS and ACC gene expression in adipose tissue. Combined with HFD, AS increased triacylglycerol circulating levels, improved insulin sensitivity and glycemic control in mice.

SIGNIFICANCE

Our findings indicated that HFD and AS can interact to modulates glycemic control and lipid profile by a mechanism potentially related with a reprogramming of genes expression in organs such as the pancreas, adipose tissue and skeletal muscle.

摘要

目的

尽管合成代谢类固醇(AS)和反式脂肪酸过载会产生全身毒性,并且是代谢和心血管疾病的独立危险因素,但它们之间的相互作用仍知之甚少。因此,我们研究了富含反式脂肪酸的饮食(HFD)与 AS 联合对血糖控制、血脂谱、脂肪组织、骨骼肌和胰腺微观结构以及参与能量代谢的基因表达的影响。

主要方法

48 只 C57BL/6 小鼠随机分为 6 组,分别用标准饮食(SD)或富含 C18:1 反式异构体的饮食(HFD)处理 12 周,单独或联合使用 10 或 20mg/kg 睾丸酮环戊丙酸(AS)。

主要发现

我们的结果表明,AS 改善了血糖控制,上调了骨骼肌中 Glut-4 和 CPT-1、脂肪组织中 FAS、ACC 和 UCP-1 的基因表达。AS 还降低了 SD 喂养小鼠的总胆固醇和 LDL 胆固醇。当与 HFD 联合使用时,AS 无法诱导脂肪组织、胰腺胰岛和β细胞的微观结构适应,但增强了 GCK 和 Glut-2(胰腺)和 Glut-4 和 CPT-1(骨骼肌)的上调。HFD 加 AS 还下调了脂肪组织中 FAS 和 ACC 的基因表达。与 HFD 联合使用时,AS 增加了循环三酰甘油水平,改善了小鼠的胰岛素敏感性和血糖控制。

意义

我们的研究结果表明,HFD 和 AS 可以相互作用,通过一种可能与胰腺、脂肪组织和骨骼肌等器官的基因表达重新编程相关的机制来调节血糖控制和血脂谱。

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