Abstract
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.
Highlights
The enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active forms in vivo
Effect of dietary fatty acid composition on bodyweight gain and insulin resistance Body weight gain increased significantly by Trans fatty acids (TFAs) and saturated fatty acids (SFAs) rich diet-fed rats compared to polyunsaturated fatty acids (PUFA) rich diet-fed rats (Table 2)
Effect of dietary fatty acid composition on 11b-HSD1 gene expression Our main aim was to determine whether 11b-HSD1 gene expression in rat adipose tissue was altered in response to chronic dietary feeding of TFA, SFA and PUFA rich diets. 11-bHSD1 mRNA levels increased significantly by 78.5% and 214% in RPWAT of SFA and TFA rich diet-fed rats respectively compared to those observed in PUFA-rich diet-fed rats (Fig. 1A&1D)
Summary
The enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active forms in vivo. Dietary fatty acids play an important role in cellular physiology by altering membrane fluidity, signal transduction and gene expression. They are implicated in the development of metabolic syndrome (visceral obesity, insulin resistance, type 2 diabetes mellitus, dyslipidemia, hypertension, and increased cardiovascular risk profile). Trans fatty acids (TFAs) and saturated fatty acids (SFAs) are reported to play an important role in the development of obesity and insulin resistance [6,7,8]. As 11b-HSD1 plays a key role in the adipose tissue metabolism and development of metabolic syndrome, a study was designed to assess the impact of dietary fats with high TFAs, SFAs and PUFAs contents on the expression of 11b-HSD1 in rat adipose tissue
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