11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to active cortisol, has become an emerging therapeutic target for type 2 diabetes mellitus and obesity.
A novel SNP, rs3753519, was strongly associated with obesity and this SNP was the only statistically significant HSD11B1 gene SNP remaining after a Bonferroni correction (odds ratio=1.97 for allelic effect, 95% confidence interval 1.23-3.16; P=0.004 and Bonferroni corrected P=0.046).
Different responsiveness in body weight and hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 mrna to 11beta-HSD inhibition by glycyrrhetinic acid treatment in obese and lean zucker rats.
However, weak associations between HSD11B1 genotype, increased 11beta-HSD1 activity, and W:H ratio suggest that polymorphic variability at the HSD11B1 locus may influence susceptibility to central obesity through enhanced 11beta-HSD1 activity (E to F conversion) in visceral adipose tissue.
It has been reported that too much cortisol or overexpression of HSD11B1 induces obesity and the insulin resistance that accompanies metabolic syndrome in rodent adipose tissue.
Our objective was to investigate a functional polymorphism in HSD11B1 (T-->G in the third intron rs12086634, which associates with lower 11beta-HSD1 activity) in PCOS with and without obesity.
Polymorphisms in 11-β hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) have been reported to be associated with obesity-related cardiovascular risk factors, such as type II diabetes and hypertension.
Polymorphisms in HSD11B1, the gene encoding 11β-hydroxysteroid dehydrogenase type 1 enzyme, have been associated with obesity, metabolic syndrome, and type 2 diabetes.
Regeneration of active glucocorticoids within liver and adipose tissue by the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) may be of pathophysiological importance in obesity and metabolic syndrome and is a therapeutic target in type 2 diabetes.
Regeneration of cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) within liver and adipose tissue may be of pathophysiological importance in obesity and the metabolic syndrome. single nucleotide polymorphisms (SNPs) in HSD11B1, the gene encoding 11β-HSD1, have been associated with type 2 diabetes and hypertension in population-based cohort studies, and with hyperandrogenism in patients with the polycystic ovary syndrome (PCOS).
Several selective 11βHSD1 inhibitors have now been developed and shown to improve metabolic dysfunction in patients with type 2 diabetes, but the small magnitude of the glucose-lowering effect has precluded their further commercial development.This review focuses on the role of 11βHSD1 as a tissue-specific regulator of cortisol exposure in obesity and type 2 diabetes in humans.
Studies have implicated 11β-HSD1 in metabolic diseases including type 2 diabetes and obesity, as well as stress-related disorders and neurodegenerative diseases, such as depression and Alzheimer's disease (AD).
The activity of the glucocorticoid activating enzyme, 11β-hydroxysteroid dehydrogenase type-1 (11βHSD1) is altered in diseases such as obesity, inflammation and psychiatric disorders.
The current obesity epidemic, however, is not characterized by increased plasma cortisol concentrations, but instead comes along with chronic low-grade inflammation in adipose tissue and concomitant increased levels of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1, gene HSD11B1), a parameter known to cause obesity in a mouse model.
The impact of adipose tissue cortisol reactivation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on markers of obesity and IR was assessed in PCOS patients.
The mechanism of this up-regulation remains uncertain; polymorphisms in the HSD11B1 gene have been associated with metabolic complications of obesity, including hypertension and type 2 diabetes, but not with obesity per se.
The overexpression of liver reductases in obesity could be an adaptive response to an increase in cortisol production by the liver and visceral 11β-HSD1 to avoid systemic hypercortisolism.
The steadily increasing epidemic of obesity continues at alarming rates, is an important public health problem, and expression changes of S100A16 and 11 β-hydroxysteroid dehydrogenase type 1(11β-HSD1) is attributable to the adipocyte differentiation.