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Obesity Surgery

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01-08-2018 | Original Contributions

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

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

Published in: Obesity Surgery | Issue 8/2018

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.

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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

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.CrossRefPubMed

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

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

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

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

23.

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

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

32.

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

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.CrossRefPubMed

34.

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

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

38.

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

Title: Sleeve Gastrectomy Reversed Obesity-Induced Hypogonadism in a Rat Model by Regulating Inflammatory Responses in the Hypothalamus and Testis
Authors: Jun Xiang
Cuidong Bian
Xiaodong Wan
Qimin Zhang
Shengsong Huang
Denglong Wu
Publication date: 01-08-2018
Publisher: Springer US
Published in: Obesity Surgery / Issue 8/2018
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI: https://doi.org/10.1007/s11695-018-3150-y

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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