Department of Zoology, University of Allahabad, Allahabad 211002, India.
Department of Zoology, University of Allahabad, Allahabad 211002, India.
Reprod Toxicol. 2024 Jan;123:108498. doi: 10.1016/j.reprotox.2023.108498. Epub 2023 Nov 10.
Neurotensin (NTS), a tridecapeptide of the gastrointestinal tract, has been implicated in the facilitation of lipid absorption on ingestion of a high-fat diet (HFD) especially via NTS receptors, NTSR1, NTSR2, and NTSR3, to cause lipid metabolic dysregulation and imbalance of the oxidant-antioxidant system. Oxidative stress induced a negative impact on reproductive function, affecting the reproductive organ and related reproductive hormones. The present study elucidated the efficacy of NTSR1 antagonist SR48692 in the modulation of HFD-induced reproductive impairment in male mice. Swiss albino mice (male, 23 ± 2 g) were maintained (6/group) for eight weeks; Group-I chow diet (CD), Group-II HFD, Group-III (HFD+SR48692), Group-IV (HFD+SR48692), Group-V (CD+SR48692) and Group-VI (CD+SR48692). SR48692 low (100 µg/kg b.w./SR48692) and high-dose (400 µg/kg b.w./SR48692) were given intraperitoneally for the last four weeks. Treatment with low-dose (SR48692) to HFD-fed mice showed some efficacy in mitigating lipid dysregulation, oxidative stress, and reproductive impairment as evidenced by decreased triglycerides, total cholesterol, low-density lipoprotein cholesterol, leptin, and increased high-density lipoprotein cholesterol, increased antioxidant defense enzymes, reduction of histopathological scores in testis and increase in plasma level of LH, FSH and testosterone compared to that of HFD, but not up to CD. With the high-dose of antagonist (SR48692) showed more adverse effects even from that of HFD. Treatment of both doses of SR48692 to CD-fed mice these effects become more extended. Less effectiveness of NTSR1 antagonist with the doses tried (low and high) in normalizing the lipid dysregulation and reproductive impairments might be due to the persistence of NTSR2/NTSR3-mediated lipid absorption.
神经降压素（NTS）是一种胃肠道中的十三肽，已被牵连到促进高脂肪饮食（HFD）摄入时的脂质吸收，特别是通过 NTS 受体 NTSR1、NTSR2 和 NTSR3，导致脂质代谢失调和氧化还原系统失衡。氧化应激对生殖功能产生负面影响，影响生殖器官和相关生殖激素。本研究阐明了 NTSR1 拮抗剂 SR48692 对雄性小鼠 HFD 诱导的生殖损伤的调节作用。瑞士白化雄性小鼠（23±2g）维持 8 周；第 I 组为标准饮食（CD），第 II 组为高脂肪饮食（HFD），第 III 组（HFD+SR48692），第 IV 组（HFD+SR48692），第 V 组（CD+SR48692）和第 VI 组（CD+SR48692）。最后四周，腹腔内给予低剂量（SR48692，100µg/kg b.w./SR48692）和高剂量（400µg/kg b.w./SR48692）。与 HFD 相比，低剂量（SR48692）处理 HFD 喂养的小鼠在缓解脂质失调、氧化应激和生殖损伤方面显示出一定的疗效，表现为甘油三酯、总胆固醇、低密度脂蛋白胆固醇、瘦素降低，高密度脂蛋白胆固醇升高，抗氧化防御酶增加，睾丸组织学评分降低，血浆 LH、FSH 和睾酮水平升高，但不如 CD。高剂量拮抗剂（SR48692）的作用甚至比 HFD 更差。两种剂量的 SR48692 处理 CD 喂养的小鼠，这些作用更加明显。NTSR1 拮抗剂在正常化脂质失调和生殖损伤方面的效果较低（低和高），可能是由于 NTSR2/NTSR3 介导的脂质吸收持续存在。
