11-Hydroxy-beta-steroid dehydrogenase gene expression in canine adipose tissue and adipocytes: Stimulation by lipopolysaccharide and tumor necrosis factor alpha

作者：Ryan V H; Trayhurn P; Hunter L; Morris P J; German A J^*

来源：Domestic Animal Endocrinology, 2011, 41(3): 150-161.

DOI：10.1016/j.domaniend.2011.06.001

• Corticosteroid
• Adipokine
• Dog
• Inflammation

The enzyme 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD-1) is expressed in a number of tissues in rodents and humans and is responsible for the reactivation of inert cortisone into cortisol. Its gene expression and activity are increased in white adipose tissue (WAT) from obese humans and may contribute to the adverse metabolic consequences of obesity and the metabolic syndrome. The extent to which 11 beta-Hso-1 contributes to adipose tissue function in dogs is unknown; the aim of the present study was to examine 11 beta-HSD-1 gene expression and its regulation by proinflammatory and anti-inflammatory agents in canine adipocytes. Real-time PCR was used to examine the expression of 11 beta-HSD-1 in canine adipose tissue and canine adipocytes differentiated in culture. The mRNA encoding 11 beta-HSD-1 was identified in all the major WAT depots in dogs and also in liver, kidney, and spleen. Quantification by real-time PCR showed that 1 mRNA was least in perirenal and falciform depots and greatest in subcutaneous, omental, and gonadal depots. Greater expression was seen in the omental depot in female than in male dogs (P = 0.05). Gene expression for 11 beta-HSD-1 was also seen in adipocytes, from both subcutaneous and visceral depots, differentiated in culture; expression was evident throughout differentiation but was generally greatest in preadipocytes and during early differentiation, declining as cells progressed to maturity. The inflammatory mediators lipopolysaccharide and tumor necrosis factor alpha had a main stimulatory effect on 11 beta-HSD-1 gene expression in canine subcutaneous adipocytes, but IL-6 had no significant effect. Treatment with dexamethasone resulted in a significant time- and dose-dependent increase in 11 beta-HSD-1 gene expression, with greatest effects seen at 24 h (2nM: approximately 4-fold; 20nM: approximately 14-fold; P = 0.010 for both). When subcutaneous adipocytes were treated with the peroxisome proliferator activated receptor gamma agonist rosiglitazone, similar dose- and time-dependent effects were noted. However, no effects were seen when adipocytes from the gonadal WAT depot were treated with rosiglitazone. The induction of 11 beta-HSD-1 expression, by the pro-inflammatory cytokine tumor necrosis factor a and by lipopolysaccharide may have implications for the pathogenesis of obesity and its associated diseases in the dog.

• 出版日期2011-10