11β-hydroxysteroid Dehydrogenase Type 1 Gene Knockout Prevents the Development of Metabolic Syndrome in C57BL/6J mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 685-694-Mechanisms of Obesity
Basic
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-686
Hanze Du, Ying Wang, Wei Wang, Kabirullah Lutfy, Desean Lovell Lee, Theodore C Friedman and Yan Jun Liu*
Charles R. Drew University of Medicine and Science, Los Angeles, CA
Obesity has now reached epidemic prevalence and dramatically increases the risk of developing insulin resistance, type 2 diabetes (T2D), and the metabolic syndrome. Pre-receptor activation of glucocorticoids (GC) via 11β-hydroxysteroid Dehydrogenase Type 1 (11βHSD1) has been identified as an important mediator of metabolic syndrome. To test the efficiency of reducing adipose 11βHSD1 production to treat visceral obesity and insulin resistance, we targeted the 11βHSD1 gene in vivo using 11βHSD1 siRNA and explored the impact of 11βHSD1on tissue-specific GC action and the phenotype of GC-induced metabolic syndrome in C57BL/6J mice. We observed that prolonged explourse of mice to exogenous GCs exhibited pronounced visceral obesity and insulin resistance with induction of adipose H6PDH and 11βHSD1 production. 11βHSD1 siRNA treatment markedly reduced adipose 11β-HSD1 mRNA and protein levels and improved the phenotype of GCs-induced obesity and insulin resistance. These findings implicated the contribution of preceptor amplification of adipose GC action to diabetic syndrome and effectively reduced 11β-HSD1 can improve the diabetogenic effects of GCs in obese diabetic mice.

Nothing to Disclose: HD, YW, WW, KL, DLL, TCF, YJL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH/NIDDK SC1DK087655 grant