The influence of the aromatase enzyme on the chronic fat-sparing effects of testosterone requires further elucidation. Our purpose was to determine whether chronic anastrozole (AN; aromatase inhibitor) treatment alters testosterone-mediated lipolytic/lipogenic gene expression in visceral fat. 10 month old F344 rats (n=6/group) received SHAM surgery, orchiectomy(ORX), ORX+testosterone-enanthate(TEST; 7.0mg/week), or ORX+TEST+AN(0.5mg/day), with drug treatment beginning 14 days post-surgery. At day 42, ORX animals exhibited nearly undetectable serum testosterone and 29% higher retroperitoneal fat mass versus SHAM (p<0.001). Testosterone treatment produced a ~380-415% higher serum testosterone versus SHAM (p<0.001) and completely prevented ORX-induced visceral fat gain (p<0.001). Retroperitoneal fat was 21% and 16% lower in ORX+TEST versus SHAM (p<0.001) and ORX+TEST+AN (p=0.007), while serum estradiol was 62% (p=0.024) and 87% (p=0.010) higher, respectively. ORX stimulated lipogenic-related gene expression in visceral fat, demonstrated by ~84-154% higher SREBP-1 (p=0.023), FASN (p=0.01), and LPL mRNA (p<0.001) versus SHAM, effects that were completely prevented in ORX+TEST animals (p<0.01 versus ORX for all). FASN (p=0.061, trend) and LPL mRNA (p=0.043) were lower in ORX+TEST+AN versus ORX and not different than SHAM, but remained higher than ORX+TEST (p<0.05). In contrast, the ORX-induced elevation in SREBP-1 mRNA was not prevented by TEST+AN, with SREBP-1 expression remaining ~117-171% higher than SHAM and ORX+TEST (p<0.01). Across groups, visceral fat mass and lipogenic-related gene expressions were negatively associated with serum testosterone, but not estradiol. Aromatase inhibition constrains testosterone-induced visceral fat loss and the down-regulation of key lipogenic genes at the mRNA level, indicating that estradiol influences the visceral fat-sparing effects of testosterone.
- aromatase inhibition
- Copyright © 2016, Journal of Applied Physiology