Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania PO, Hyderabad-500 604, Andhra Pradesh, India.
Lipids Health Dis. 2010 Oct 8;9:111. doi: 10.1186/1476-511X-9-111.
The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active forms in vivo. Adipose-specific overexpression of 11β-HSD1 induces metabolic syndrome in mice, whereas 11β-HSD1 null mice are resistant to it. Dietary trans and saturated fatty acids (TFAs and SFAs) are involved in the development of metabolic syndrome, whereas polyunsaturated fatty acids (PUFA) offer protection against this. Here, we report the effects of chronic feeding of different diets containing vanaspati (TFA rich), palm oil (SFA rich) and sunflower oil (PUFA rich) at 10%level on 11β-HSD1 gene expression in rat retroperitoneal adipose tissue. 11β-HSD1 gene expression was significantly higher in TFA rich diet-fed rats compared to SFA rich diet-fed rats, which in turn was significantly higher than PUFA rich diet-fed rats. Similar trend was observed in the expression of CCAAT-enhancer binding protein-α (C/EBP-α), the main transcription factor required for the expression of 11β-HSD1. We propose that TFAs and SFAs increase local amplification of glucocorticoid action in adipose tissue by upregulating 11β-HSD1 by altering C/EBP-α-gene expression. The increased levels of glucocorticoids in adipose tissue may lead to development of obesity and insulin resistance, thereby increasing the risk of developing metabolic syndrome.
11β-羟类固醇脱氢酶 1 型（11β-HSD1）可将无活性的糖皮质激素在体内转化为其活性形式，从而放大细胞内糖皮质激素的作用。脂肪组织特异性过表达 11β-HSD1 可诱导小鼠发生代谢综合征，而 11β-HSD1 基因敲除小鼠则对此具有抗性。反式和饱和脂肪酸（TFAs 和 SFAs）与代谢综合征的发生有关，而多不饱和脂肪酸（PUFAs）则对此具有保护作用。本研究报告了以 10%的水平用不同饮食（富含 TFA 的凡士达、富含 SFA 的棕榈油和富含 PUFA 的葵花籽油）慢性喂养大鼠对大鼠腹膜后脂肪组织中 11β-HSD1 基因表达的影响。与富含 SFA 的饮食喂养的大鼠相比，富含 TFA 的饮食喂养的大鼠中 11β-HSD1 基因的表达显著升高，而后者又明显高于富含 PUFA 的饮食喂养的大鼠。C/EBP-α（11β-HSD1 表达的主要转录因子）的表达也观察到了类似的趋势。我们提出，TFAs 和 SFAs 通过改变 C/EBP-α 基因表达而上调 11β-HSD1，从而增加脂肪组织中糖皮质激素作用的局部放大。脂肪组织中糖皮质激素水平的升高可能导致肥胖和胰岛素抵抗的发生，从而增加代谢综合征的发病风险。
