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Sleeve Gastrectomy Reversed Obesity-Induced Hypogonadism in a Rat Model by Regulating Inflammatory Responses in the Hypothalamus and Testis

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Abstract

Background

Obesity is a metabolic disease with a serious health burden in children and adults, and it induces a variety of conditions including subfecundity. Sleeve gastrectomy showed encouraging results in terms of weight loss and improve quality of life, and this study aimed to determine whether sleeve gastrectomy could reverse obesity-induced impaired fertility in male Sprague–Dawley rats.

Methods

After 16 weeks of a chow diet (CD) or a high-fat diet (HFD) challenge, rats on the HFD were given a sleeve gastrectomy or sham operation and then fed an HFD for another 8 weeks. Serum glucose, insulin, lipids, sex hormone, sperm quality, inflammatory profile of the testis, and hypothalamic Kiss1 expression in the three study groups were compared.

Results

Sleeve gastrectomy significantly decreased HFD-induced obesity and serum glucose and insulin levels. It also reversed the HFD-induced increase in teratozoospermia and decreases in sperm motility and progressive motility. Testicular morphological abnormalities were also improved after sleeve gastrectomy. Enzyme-linked immunosorbent assay showed that the expression of sex hormones increased after sleeve gastrectomy and that expression of inflammatory factors decreased. The HFD induced a hypothalamic inflammatory response that inhibited Kiss1 expression, which in turn mediated sex hormone expression. Sleeve gastrectomy treatment improved the hypothalamic response.

Conclusions

The results consistently showed that sleeve gastrectomy reversed obesity-induced male fertility impairment by decreasing the inflammatory responses of the testis and hypothalamus.

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References

  1. Du Plessis SS, Cabler S, McAlister DA, et al. The effect of obesity on sperm disorders and male infertility. Nat Rev Urol. 2010;7(3):153–61.

    Article  PubMed  Google Scholar 

  2. Nathan PC, Jovcevska V, Ness KK, et al. The prevalence of overweight and obesity in pediatric survivors of cancer. J Pediatr. 2006;149(4):518–25.

    Article  PubMed  Google Scholar 

  3. Berzigotti A, Albillos A, Villanueva C, et al. Effects of an intensive lifestyle intervention program on portal hypertension in patients with cirrhosis and obesity: the Sportdiet Study. Hepatology. 2017;65(4):1293–305.

    Article  PubMed  Google Scholar 

  4. Lavie CJ, Arena R, Alpert MA, et al. Management of cardiovascular diseases in patients with obesity. Nat Rev Cardiol. 2017;15:45–56.

    Article  PubMed  Google Scholar 

  5. Barrett K, Chang YP. Behavioral interventions targeting chronic pain, depression, and substance use disorder in primary care. J Nurs Scholarsh. 2016;48(4):345–53.

    Article  PubMed  Google Scholar 

  6. Zain MM, Norman RJ. Impact of obesity on female fertility and fertility treatment. Womens Health(Lond). 2008;4(2):183–94.

    Google Scholar 

  7. Gesink Law DC, Maclehose RF, Longnecker MP. Obesity and time to pregnancy. Hum Reprod. 2007;22(2):414–20.

    Article  PubMed  CAS  Google Scholar 

  8. Hammoud AO, Wilde N, Gibson M, et al. Male obesity and alteration in sperm parameters. Fertil Steril. 2008;90(6):2222–5.

    Article  PubMed  Google Scholar 

  9. Hofny ER, Ali ME, Abdel-Hafez HZ, et al. Semen parameters and hormonal profile in obese fertile and infertile males. Fertil Steril. 2010;94(2):581–4.

    Article  PubMed  CAS  Google Scholar 

  10. Hammiche F, Laven JS, Twigt JM, et al. Body mass index and central adiposity are associated with sperm quality in men of subfertile couples. Hum Reprod. 2012;27(8):2365–72.

    Article  PubMed  Google Scholar 

  11. Abiad, F., J. Awwad, H. A. Abbas et al. Management of weight loss in obesity-associated male infertility: a spotlight on bariatric surgery. Hum Fertil(Camb). 2017;1–9.

  12. Skurk T, Alberti-Huber C, Herder C, et al. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007;92(3):1023–33.

    Article  PubMed  CAS  Google Scholar 

  13. Sabanayagam C, Liew G, Tai ES, et al. Relationship between glycated haemoglobin and microvascular complications: is there a natural cut-off point for the diagnosis of diabetes? Diabetologia. 2009;52(7):1279–89.

    Article  PubMed  CAS  Google Scholar 

  14. Yang, J., C. S. Kim, T. H. Tu et al. Quercetin protects obesity-induced hypothalamic inflammation by reducing microglia-mediated inflammatory responses via Ho-1 induction. Nutrients. 2017;9 no. 7.

  15. Hussain MA, Song WJ, Wolfe A. There is kisspeptin—and then there is kisspeptin. Trends Endocrinol Metab. 2015;26(10):564–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Hankir MK, Seyfried F, Hintschich CA, et al. Gastric bypass surgery recruits a gut Ppar-alpha-striatal D1r pathway to reduce fat appetite in obese rats. Cell Metab. 2017;25(2):335–44.

    Article  PubMed  CAS  Google Scholar 

  17. Paranjape SA, Chan O, Zhu W, et al. Improvement in hepatic insulin sensitivity after Roux-En-Y gastric bypass in a rat model of obesity is partially mediated via hypothalamic insulin action. Diabetologia. 2013;56(9):2055–8.

    Article  PubMed  CAS  Google Scholar 

  18. Hu E, Kim JB, Sarraf P, et al. Inhibition of adipogenesis through map kinase-mediated phosphorylation of Ppargamma. Science. 1996;274(5295):2100–3.

    Article  PubMed  CAS  Google Scholar 

  19. Tong G, Krauss A, Mochner J, et al. Deep hypothermia therapy attenuates Lps-induced microglia neuroinflammation via the Stat3 pathway. Neuroscience. 2017;358:201–10.

    Article  PubMed  CAS  Google Scholar 

  20. Qin H, Yeh WI, De Sarno P, et al. Signal transducer and activator of transcription-3/suppressor of cytokine signaling-3 (Stat3/Socs3) Axis in myeloid cells regulates neuroinflammation. Proc Natl Acad Sci U S A. 2012;109(13):5004–9.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pielecka-Fortuna J, Chu Z, Moenter SM. Kisspeptin acts directly and indirectly to increase gonadotropin-releasing hormone neuron activity and its effects are modulated by estradiol. Endocrinology. 2008;149(4):1979–86.

    Article  PubMed  CAS  Google Scholar 

  22. Merkley CM, Coolen LM, Goodman RL, et al. Evidence for changes in numbers of synaptic inputs onto Kndy and Gnrh Neurones during the preovulatory Lh surge in the ewe. J Neuroendocrinol. 2015;27(7):624–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Hammoud AO, Gibson M, Peterson CM, et al. Obesity and male reproductive potential. J Androl. 2006;27(5):619–26.

    Article  PubMed  Google Scholar 

  24. Fan Y, Liu Y, Xue K, et al. Diet-induced obesity in male C57bl/6 mice decreases fertility as a consequence of disrupted blood-testis barrier. PLoS One. 2015;10(4):e0120775.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Chavarro JE, Toth TL, Wright DL, et al. Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril. 2010;93(7):2222–31.

    Article  PubMed  CAS  Google Scholar 

  26. Giagulli VA, Kaufman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab. 1994;79(4):997–1000.

    PubMed  CAS  Google Scholar 

  27. Aggerholm AS, Thulstrup AM, Toft G, et al. Is overweight a risk factor for reduced semen quality and altered serum sex hormone profile? Fertil Steril. 2008;90(3):619–26.

    Article  PubMed  CAS  Google Scholar 

  28. Pauli EM, Legro RS, Demers LM, et al. Diminished paternity and gonadal function with increasing obesity in men. Fertil Steril. 2008;90(2):346–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Hammoud AO, Gibson M, Peterson CM, et al. Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril. 2008;90(4):897–904.

    Article  PubMed  Google Scholar 

  30. Fariello RM, Pariz JR, Spaine DM, et al. Association between obesity and alteration of sperm DNA integrity and mitochondrial activity. BJU Int. 2012;110(6):863–7.

    Article  PubMed  CAS  Google Scholar 

  31. Bakos HW, Mitchell M, Setchell BP, et al. The effect of paternal diet-induced obesity on sperm function and fertilization in a mouse model. Int J Androl. 2011;34(5 Pt 1):402–10.

    Article  PubMed  CAS  Google Scholar 

  32. Azenabor A, Ekun AO, Akinloye O. Impact of inflammation on male reproductive tract. J Reprod Infertil. 2015;16(3):123–9.

    PubMed  PubMed Central  Google Scholar 

  33. Bhandari P, Rishi P, Prabha V. Positive effect of probiotic Lactobacillus plantarum in reversing the Lps induced infertility in mouse model. J Med Microbiol. 2016;65:345–50.

    Article  PubMed  CAS  Google Scholar 

  34. Oakley AE, Clifton DK, Steiner RA. Kisspeptin signaling in the brain. Endocr Rev. 2009;30(6):713–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. de Roux N, Genin E, Carel JC, et al. Hypogonadotropic hypogonadism due to loss of function of the Kiss1-derived peptide receptor Gpr54. Proc Natl Acad Sci U S A. 2003;100(19):10972–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Seminara SB, Messager S, Chatzidaki EE, et al. The Gpr54 gene as a regulator of puberty. N Engl J Med. 2003;349(17):1614–27.

    Article  PubMed  CAS  Google Scholar 

  37. d’Anglemont de Tassigny X, Fagg LA, Dixon JP, et al. Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. Proc Natl Acad Sci U S A. 2007;104(25):10714–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Lapatto R, Pallais JC, Zhang D, et al. Kiss1−/− mice exhibit more variable hypogonadism than Gpr54−/− mice. Endocrinology. 2007;148(10):4927–36.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Urinary Surgery, Tongji Hospital, Tongji University School of Medicine, 389 Xin-Cun Road, Shanghai, 200065, China

    Jun Xiang, Cuidong Bian, Xiaodong Wan, Qimin Zhang, Shengsong Huang & Denglong Wu

Authors
  1. Jun Xiang
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  2. Cuidong Bian
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  3. Xiaodong Wan
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  4. Qimin Zhang
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  5. Shengsong Huang
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  6. Denglong Wu
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Corresponding authors

Correspondence to Jun Xiang or Denglong Wu.

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The authors declare that they have no conflict of interest.

Ethical Approval Statement

All animals were treated in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments and animal procedures were approved by the Animal Care and Utilization Committee of Tongji Hospital and performed following the guidelines of the Tongji Hospital Ethics Committee.

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Jun Xiang and Cuidong Bian are co-first authors.

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Xiang, J., Bian, C., Wan, X. et al. Sleeve Gastrectomy Reversed Obesity-Induced Hypogonadism in a Rat Model by Regulating Inflammatory Responses in the Hypothalamus and Testis. OBES SURG 28, 2272–2280 (2018). https://doi.org/10.1007/s11695-018-3150-y

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  • DOI: https://doi.org/10.1007/s11695-018-3150-y

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