PMID- 27539493 OWN - NLM STAT- Publisher LR - 20191120 IS - 1522-1601 (Electronic) IS - 0161-7567 (Linking) VI - 121 IP - 3 DP - 2016 Sep 1 TI - Testosterone inhibits expression of lipogenic genes in visceral fat by an estrogen-dependent mechanism. PG - 792-805 LID - 10.1152/japplphysiol.00238.2016 [doi] AB - 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, an aromatase inhibitor) treatment alters testosterone-mediated lipolytic/lipogenic gene expression in visceral fat. Ten-month-old Fischer 344 rats (n = 6/group) were subjected to sham surgery (SHAM), orchiectomy (ORX), ORX + treatment with testosterone enanthate (TEST, 7.0 mg/wk), or ORX + TEST + AN (0.5 mg/day), with drug treatment beginning 14 days postsurgery. At day 42, ORX animals exhibited nearly undetectable serum testosterone and 29% higher retroperitoneal fat mass than SHAM animals (P < 0.001). TEST produced a approximately 380-415% higher serum testosterone than 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 than SHAM (P < 0.001) and ORX + TEST + AN (P = 0.007) animals, while serum estradiol (E(2)) was 62% (P = 0.024) and 87% (P = 0.010) higher, respectively. ORX stimulated lipogenic-related gene expression in visceral fat, demonstrated by approximately 84-154% higher sterol regulatory element-binding protein-1 (SREBP-1, P = 0.023), fatty acid synthase (P = 0.01), and LPL (P < 0.001) mRNA than SHAM animals, effects that were completely prevented in ORX + TEST animals (P < 0.01 vs. ORX for all). Fatty acid synthase (P = 0.061, trend) and LPL (P = 0.043) mRNA levels were lower in ORX + TEST + AN than ORX animals and not different from SHAM animals but remained higher than in ORX + TEST animals (P < 0.05). In contrast, the ORX-induced elevation in SREBP-1 mRNA was not prevented by TEST + AN, with SREBP-1 expression remaining approximately 117-171% higher than in SHAM and ORX + TEST animals (P < 0.01). Across groups, visceral fat mass and lipogenic-related gene expression were negatively associated with serum testosterone, but not E(2) Aromatase inhibition constrains testosterone-induced visceral fat loss and the downregulation of key lipogenic genes at the mRNA level, indicating that E(2) influences the visceral fat-sparing effects of testosterone. FAU - Holland, A Maleah AU - Holland AM AD - School of Kinesiology, Auburn University, Auburn, Alabama; FAU - Roberts, Michael D AU - Roberts MD AD - School of Kinesiology, Auburn University, Auburn, Alabama; Department of Cell Biology and Physiology, Edward Via College of Osteopathic Medicine-Auburn Campus, Auburn, Alabama. FAU - Mumford, Petey W AU - Mumford PW AD - School of Kinesiology, Auburn University, Auburn, Alabama; FAU - Mobley, C Brooks AU - Mobley CB AD - School of Kinesiology, Auburn University, Auburn, Alabama; FAU - Kephart, Wesley C AU - Kephart WC AD - School of Kinesiology, Auburn University, Auburn, Alabama; FAU - Conover, Christine F AU - Conover CF AD - Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; FAU - Beggs, Luke A AU - Beggs LA AD - Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida; and. FAU - Balaez, Alexander AU - Balaez A AD - Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida; and. FAU - Otzel, Dana M AU - Otzel DM AD - Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida; and. FAU - Yarrow, Joshua F AU - Yarrow JF AD - Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida; and. FAU - Borst, Stephen E AU - Borst SE AD - Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida; and. FAU - Beck, Darren T AU - Beck DT AD - School of Kinesiology, Auburn University, Auburn, Alabama; Department of Cell Biology and Physiology, Edward Via College of Osteopathic Medicine-Auburn Campus, Auburn, Alabama dbeck@auburn.vcom.edu. LA - eng PT - Journal Article DEP - 20160818 PL - United States TA - J Appl Physiol (1985) JT - Journal of applied physiology (Bethesda, Md. : 1985) JID - 8502536 OTO - NOTNLM OT - adipose OT - androgen OT - aromatase OT - estrogen OT - steroids EDAT- 2016/08/20 06:00 MHDA- 2016/08/20 06:00 CRDT- 2016/08/20 06:00 PHST- 2016/03/16 00:00 [received] PHST- 2016/08/15 00:00 [accepted] PHST- 2016/08/20 06:00 [entrez] PHST- 2016/08/20 06:00 [pubmed] PHST- 2016/08/20 06:00 [medline] AID - japplphysiol.00238.2016 [pii] AID - 10.1152/japplphysiol.00238.2016 [doi] PST - ppublish SO - J Appl Physiol (1985). 2016 Sep 1;121(3):792-805. doi: 10.1152/japplphysiol.00238.2016. Epub 2016 Aug 18.