Testosterone replacement alters the cell size in visceral fat but not in subcutaneous fat in hypogonadal aged male rats as a late-onset hypogonadism animal model

Abstract

Amr Abdelhamed,1,2 Shin-ichi Hisasue,1 Masato Shirai,3 Kazuhito Matsushita,1 Yoshiaki Wakumoto,1 Akira Tsujimura,1 Taiji Tsukamoto,4 Shigeo Horie1 1Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo, Japan; 2Department of Dermatology, Venereology and Andrology, Sohag University, Graduate School of Medicine, Sohag, Egypt; 3Department of Urology, Juntendo University Urayasu Hospital, Urayasu, Japan; 4Department of Urology, School of Medicine, Sapporo Medical University, Sapporo, Japan Background: Patients with late-onset hypogonadism (LOH) benefit from testosterone replacement by improvement in the parameters of the metabolic syndrome, but fat cell morphology in these patients is still unclear. This study aims to determine the effect of testosterone replacement on the morphology of fat cells in subcutaneous and visceral adipose tissue and on erectile function in hypogonadal aged male rats as a model of LOH. Methods: Ten male Sprague-Dawley rats aged 20–22 months were randomly allocated to two groups, ie, aged male controls (control group, n=5) and aged males treated with testosterone replacement therapy (TRT group, n=5). Testosterone enanthate 25 mg was injected subcutaneously every 2 weeks for 6 weeks. At 6 weeks, the intracavernous pressure (ICP) and mean arterial blood pressure (MAP) ratio was assessed. Visceral and subcutaneous adipose tissue specimens were collected and analyzed using Image-J software. Results: Body weight at 2, 4, and 6 weeks after TRT was 800.0±35.4 g, 767.5±46.3 g, and 780±40.4 g, respectively (not statistically significant). The ICP/MAP ratio was 0.341±0.015 in the TRT group and 0.274±0.049 in the control group (not statistically significant). The median subcutaneous fat cell size was 4.85×103 (range 0.85–12.53×103) µm2 in the control group and 4.93×103 (range 6.42–19.7×103) µm2 in the TRT group (not statistically significant). In contrast, median visceral fat cell size was significantly smaller in the TRT group (4.93×103 µm2 [range 0.51–14.88×103]) than in the control group (6.08×103 µm2 [0.77–19.97×103]; P<0.001, Mann-Whitney U test). Conclusion: This is the first study clearly indicating that TRT can decrease visceral fat cell size, which is a key modulator in the metabolic syndrome. However, a short course of TRT could not improve the ICP response in hypogonadal aged male rats. Further investigation is necessary to clarify the exact rationale of TRT on the visceral fat cell. Keywords: testosterone replacement, visceral fat, erectile dysfunction, age