Session: MON 796-817-Diabetes Genetics & Epidemiology
Poster Board MON-810
Methods: Male mice (5-6 week old, n=6-10/group): 11βHSD1-deficient (Hsd11b1-/-), transgenically overexpressing 11βHSD1 in liver (LOE) or wild-type (WT) were fed chow (C; 11% fat), high fat (HF; 58% fat) or western diet (WD; 38% fat + 0.2% cholesterol) for 12 weeks. Liver and fat depots were collected, RNA extracted and analysed by qPCR. Data (corrected for housekeeping genes) are mean ±SEM.
Results: Significantly decreased liver weight was observed for WD-fed Hsd11b1-/- mice (p<0.05), and reduced mesenteric fat was observed in HF-fed LOE mice compared to WT mice on the same diet (p<0.05). Compared to chow, WD decreased hepatic levels of mRNAs encoding SREBP2, HMG-CoA-reductase and HMG-CoA-synthase in WT mice as predicted, and in LOE mice (p<0.001). Hepatic LXRa mRNA was unaffected by diet in WT and Hsd11b1-/- mice (and did not differ in chow-fed mice between genotypes), but was increased in WD-fed LOE mice (WT, 100±3.46 vs. LOE, 178.48±6.21, p<0.05), as were the LXRa targets, Abgc5/8 (Abcg5: WT, 100±4.65 vs. LOE, 242.13±9.91, p<0.001; Abcg8: WT, 100±3.23 vs. LOE, 167.77±5.49, p<0.01).
Conclusion: These data do not support a role for hepatic 11βHSD1 in de novo cholesterol synthesis. However, increased hepatic Abcg5/8 expression in WD-fed LOE mice suggests hepatic 11βHSD1 promotes sterol efflux into the intestinal and biliary lumen, possibly meditated through higher Lxra expression. This suggests a role for hepatic 11βHSD1 in promoting biliary cholesterol secretion.
Nothing to Disclose: KM, TYM, CJK, RA, KEC, JRS
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