Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
Department of Science Laboratory Technology, Akanu Ibiam Federal Polytechnic, Unwana, Afikpo, Ebonyi State, Nigeria.
Reproduction. 2020 Dec;160(6):863-872. doi: 10.1530/REP-20-0381.
Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague-Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.
肥胖及其伴随的并发症使睾丸葡萄糖代谢异常、阴茎勃起功能障碍和不育的风险增加。本研究旨在探讨奥利司他在改善高脂肪饮食（HFD）诱导肥胖雄性大鼠勃起功能障碍和生育力下降方面的潜力。将 18 只体重在 250 至 300 克之间的成年雄性 Sprague-Dawley 大鼠分为三组（每组 6 只）：正常对照组（NC）、HFD 组和 HFD+奥利司他（10mg/kg 体重/天，共 12 周）（HFD+O 组）。在第 11 至 12 周期间评估了交配行为和生育参数，在第 12 周结束时评估了葡萄糖代谢参数。奥利司他增加了肥胖大鼠睾丸中葡萄糖转运蛋白（Glut1 和 Glut3）、单羧酸转运蛋白（Mct2 和 Mct4）和乳酸脱氢酶 C 型（Ldhc）的 mRNA 水平，降低了睾丸内的乳酸和葡萄糖水平以及 LDH 活性。此外，奥利司他增加了超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽-S-转移酶（GST）和谷胱甘肽还原酶（GR）的活性以及总抗氧化能力（TAC），同时降低了肥胖大鼠阴茎中的丙二醛水平。同样，奥利司他改善了肥胖大鼠的阴茎 cGMP 水平、性行为和生育力。阴茎 cGMP 水平与总交配和插入次数呈正相关，与交配/插入次数比呈负相关。奥利司他通过靶向睾丸乳酸代谢、阴茎氧化应激和性行为来改善肥胖状态下的生育潜力。因此，奥利司他显示出有希望的保护作用，并可能维持肥胖男性的生育潜力。
