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肥胖和胰岛素抵抗相关的病态肥胖患者中脂肪生成和脂肪分解基因表达的变化。

Obesity and insulin resistance-related changes in the expression of lipogenic and lipolytic genes in morbidly obese subjects.

机构信息

CIBER Fisiopatología Obesidad y Nutrición, Hospital Clínico Virgen de la Victoria, Malaga, Spain.

出版信息

Obes Surg. 2010 Nov;20(11):1559-67. doi: 10.1007/s11695-010-0194-z.

Abstract

BACKGROUND

The storage capacity of adipose tissue may be an important factor linking obesity, insulin resistance (IR), and associated morbidities. The aim of this study was to analyze the expression of lipogenic and lipolytic genes in adipose tissue and the influence of IR.

METHODS

We studied the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) and lipogenic and lipolytic enzymes in the visceral (VAT) and subcutaneous adipose tissue (SAT) from 23 morbidly obese patients (MO; 13 with low IR and ten with high IR) and from 15 healthy, lean controls.

RESULTS

In the VAT and SAT from the MO, we found an increased expression of PPARγ (p = 0.001 and p = 0.022, respectively), acyl-coenzyme A (CoA)/cholesterol acyltransferase (p < 0.001 and p < 0.001), aquaporin 7 (p < 0.001 and p = 0.003), and adipose triglyceride lipase (p < 0.001 and p < 0.001) and a reduced expression of acetyl-coenzyme A carboxylase (p = 0.004 and p < 0.001), independently of the state of IR. The expression of phosphoenolpyruvate carboxykinase and acyl-CoA synthetase, however, was significantly lower in the MO with high IR (p < 0.05). Glycerol kinase (p = 0.010), hormone-sensitive lipase (p < 0.001), and perilipin (p = 0.006) were only significantly increased in VAT. Acyl-CoA synthetase (p = 0.012) and fatty acid binding protein-4 (p = 0.003) were only significantly decreased in SAT. The expression of the genes studied was only greater in the SAT than the VAT in the controls.

CONCLUSION

Our results show an upregulation of genes facilitating triglyceride/fatty acid cycling and a reduction in the genes involved in de novo synthesis of fatty acids in morbid obesity. The expression of some of the genes studied seems to be related with the state of IR. VAT and SAT differ metabolically and also between controls and MO.

摘要

背景

脂肪组织的储存能力可能是将肥胖、胰岛素抵抗(IR)和相关疾病联系起来的一个重要因素。本研究的目的是分析脂肪组织中脂肪生成和脂肪分解基因的表达及其对 IR 的影响。

方法

我们研究了来自 23 名病态肥胖患者(MO;13 名 IR 低,10 名 IR 高)和 15 名健康瘦对照组的内脏(VAT)和皮下脂肪组织(SAT)中过氧化物酶体增殖物激活受体-γ(PPARγ)和脂肪生成和脂肪分解酶的 mRNA 表达。

结果

在 MO 的 VAT 和 SAT 中,我们发现 PPARγ 的表达增加(p=0.001 和 p=0.022),酰基辅酶 A(CoA)/胆固醇酰基转移酶(p<0.001 和 p<0.001),水通道蛋白 7(p<0.001 和 p=0.003)和脂肪甘油三酯脂肪酶(p<0.001 和 p<0.001),乙酰辅酶 A 羧化酶的表达降低(p=0.004 和 p<0.001),与 IR 状态无关。然而,IR 高的 MO 中磷酸烯醇丙酮酸羧激酶和酰基辅酶 A 合成酶的表达显著降低(p<0.05)。甘油激酶(p=0.010)、激素敏感脂肪酶(p<0.001)和 perilipin(p=0.006)仅在 VAT 中显著增加。酰基辅酶 A 合成酶(p=0.012)和脂肪酸结合蛋白-4(p=0.003)仅在 SAT 中显著降低。在对照组中,研究的基因表达仅在 SAT 中大于 VAT。

结论

我们的结果表明,在病态肥胖中,促进甘油三酯/脂肪酸循环的基因上调,参与脂肪酸从头合成的基因减少。研究的一些基因的表达似乎与 IR 状态有关。VAT 和 SAT 在代谢上以及在对照组和 MO 之间也存在差异。

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