Zhao Jing-Lu, Zhao Yu-Yun, Zhu Wei-Jie
Department of Developmental and Regenerative Biology, College of Life Science and Technology, Jinan University, Guangdong, Guangzhou 510632, China.
College of Chemical and Biological Engineering, Hunan University of Science and Engineering, Hunan, Yongzhou 425199, China.
Gen Comp Endocrinol. 2017 Oct 1;252:48-59. doi: 10.1016/j.ygcen.2017.07.013. Epub 2017 Jul 22.
The interaction between obesity and chronic inflammation has been studied. Diet-induced obesity or chronic inflammation could reduce the testicular functions of males. However, the mechanism underlying the reproductive effects of fattening foods in males with or without chronic inflammation still needs further discussion. This study was aimed to investigate the effects of high-fat, high-protein diet on testicular steroidogenesis and sperm parameters in adult mice under physiological and chronic inflammatory conditions. Because casein can trigger a non-infectious systemic inflammatory response, we used casein injection to induce chronic inflammation in male adult Kunming mice. Twenty-four mice were randomly and equally divided into four groups: (i) normal diet+saline (Control); (ii) normal diet+casein (ND+CS); (iii) high-fat, high-protein diet+saline (HFPD+SI); (iv) high-fat, high-protein diet+casein (HFPD+CS). After 8weeks, there was a significant increase in body weight for groups HFPD+SI and HFPD+CS and a decrease in group ND+CS compared with the control. The serum levels of tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10) and lipid profiles were increased markedly in groups ND+CS, HFPD+SI and HFPD+CS compared with the control. A remarkable reduction of serum adiponectin level occurred in group HFPD+CS compared with group ND+CS. Sperm parameters (sperm count, viability and abnormality) were also adversely affected in groups ND+CS and HFPD+SI. Groups ND+CS and HFPD+SI showed severe pathological changes in testicular tissues. Semiquantitative RT-PCR, Western blot and immunohistochemical staining also showed significant reductions in both testicular mRNA and protein levels of steroidogenic acute regulatory (StAR) and cytochrome P450scc (CYP11A1) in groups HFPD+SI and HFPD+CS compared with the control, whereas testicular mRNA and protein levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) in groups HFPD+SI and HFPD+CS significantly increased. The mRNA and protein levels of the StAR and 3β-HSD in group HFPD+CS were both higher than those of in group ND+CS. These results indicated that Kunming male mice with high-fat, high-protein diet and casein injection for 8weeks can be used to establish a diet-induced obesity and chronic systemic inflammation. The sperm parameters in groups ND+CS and HFPD+SI decreased accompanied by pathological changes of testicular tissue. This resultant effect of reduced serum testosterone levels was associated with the overproduction of TNF-α and IL-10 and down-regulation of StAR and CYP11A1. Under the same casein-induced chronic inflammation condition, the mice with high-fat, high-protein diet had better testicular steroidogenesis activity and sperm parameters compared with the mice in normal diet, indicating that the mice with casein-induced inflammatory injury consuming a high-fat, high-protein diet gained weight normally, reduced serum adiponectin level and increased testosterone production by an upregulation of 3β-HSD expression. High-fat, high-protein diet attenuated the negative impact of casein-induced chronic inflammation on testicular steroidogenesis and sperm parameters.
肥胖与慢性炎症之间的相互作用已得到研究。饮食诱导的肥胖或慢性炎症会降低男性的睾丸功能。然而,含高脂肪食物对有或无慢性炎症男性生殖影响的潜在机制仍需进一步探讨。本研究旨在调查在生理和慢性炎症条件下,高脂高蛋白饮食对成年小鼠睾丸类固醇生成及精子参数的影响。由于酪蛋白可引发非感染性全身炎症反应,我们通过注射酪蛋白诱导成年雄性昆明小鼠发生慢性炎症。24只小鼠被随机等分为四组:(i)正常饮食+生理盐水(对照组);(ii)正常饮食+酪蛋白(ND+CS);(iii)高脂高蛋白饮食+生理盐水(HFPD+SI);(iv)高脂高蛋白饮食+酪蛋白(HFPD+CS)。8周后,与对照组相比,HFPD+SI组和HFPD+CS组体重显著增加,ND+CS组体重下降。与对照组相比,ND+CS组、HFPD+SI组和HFPD+CS组血清肿瘤坏死因子α(TNF-α)、白细胞介素-10(IL-10)水平及血脂显著升高。与ND+CS组相比,HFPD+CS组血清脂联素水平显著降低。ND+CS组和HFPD+SI组精子参数(精子计数、活力及畸形率)也受到不利影响。ND+CS组和HFPD+SI组睾丸组织出现严重病理变化。半定量逆转录-聚合酶链反应(RT-PCR)、蛋白质免疫印迹法(Western blot)及免疫组织化学染色结果还显示,与对照组相比,HFPD+SI组和HFPD+CS组睾丸中类固醇生成急性调节蛋白(StAR)和细胞色素P450侧链裂解酶(CYP11A1)的mRNA和蛋白水平显著降低,而HFPD+SI组和HFPD+CS组睾丸中3β-羟基类固醇脱氢酶(3β-HSD)的mRNA和蛋白水平显著升高。HFPD+CS组中StAR和3β-HSD的mRNA和蛋白水平均高于ND+CS组。这些结果表明,高脂高蛋白饮食并注射酪蛋白8周的昆明雄性小鼠可用于建立饮食诱导的肥胖和慢性全身炎症模型。ND+CS组和HFPD+SI组精子参数下降,同时伴有睾丸组织病理变化。血清睾酮水平降低的这种结果效应与TNF-α和IL-10的过量产生以及StAR和CYP11A1的下调有关。在相同的酪蛋白诱导慢性炎症条件下,与正常饮食小鼠相比,高脂高蛋白饮食小鼠具有更好的睾丸类固醇生成活性和精子参数,这表明酪蛋白诱导炎症损伤的小鼠食用高脂高蛋白饮食后体重正常增加,血清脂联素水平降低,通过上调3β-HSD表达增加睾酮生成。高脂高蛋白饮食减轻了酪蛋白诱导的慢性炎症对睾丸类固醇生成和精子参数的负面影响。