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Anti-mullerian hormone attenuates insulin resistance and systemic inflammation in old obese C57BL/6 male mice

  • Research article
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Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Purpose

Epidemiological studies show that Anti-mullerian hormone (AMH) is inversely correlated with age, obesity-related diseases, and all-cause mortality in men. To further investigate the role of AMH in aging and obesity, we studied the effect of AMH treatment on the inflammatory and metabolic parameters and weight in old male C57BL/6 mice.

Method

Thirty-six old male C57BL/6 mice (18 month-old) were either on the High-Fat Diet (HFD) or Normal Diet (ND). When obesity occurred in the HFD group, each group was divided into two subgroups; AMH-treated (ND+AMH and HFD+AMH) or controls (ND and HFD). The AMH subgroup received 15 ng/gbw of recombinant AMH injection every 48 h in four weeks. Then, serum AMH, CRP, fasting glucose, fasting insulin, and HOMA-IR were measured and analyzed.

Results

AMH injection decreased CRP level (HFD =622.86±25.73, HFD+AMH =543.2±24.99 ng/ml, p= 0.003), fasting insulin (HFD=1.50± 0.34, HFD+AMH =0.8±0.25 ng/ml, p=0.006) and HOMA-IR (HFD=12.76± 2.88, HFD+AMH =7.06±2.31, p=0.008) in the obese old mice comparison with control. In ND group, just CRP levels dropped following AMH injection (ND=451.24±20.61, ND+AMH= 326.8±23.76 ng/ml; p=0.001). Accelerated weight gain was observed in HFD+AMH compared with the HFD subgroup (p<0.05).

Conclusions

In conclusion, increasing the circulating level of AMH could subside the systemic inflammation through decreasing CRP levels regardless of diet type and enhance insulin sensitivity in old obese mice. It can also lead to higher weight gain, without inflammation, in old obese male mice who are on an HFD.

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Abbreviations

AMH:

Anti-mullerian hormone

CRP:

C-reactive protein

HOMA-IR:

Homeostatic Model Assessment for Insulin Resistance

ND:

Normal Diet

HFD:

High Fat Diet

CVD:

Cardiovascular Disease

T2D:

Type 2 Diabetes

SMAD:

(Small Mothers against Decapentaplegic homolog)

References

  1. Zamboni M, Mazzali G. Obesity in the elderly: an emerging health issue. Int J Obes. 2012;36:1151–2.

    Article  CAS  Google Scholar 

  2. Sarvottam K, Yadav RK. Obesity-related inflammation & cardiovascular disease: efficacy of a yoga-based lifestyle intervention. Indian J Med Res. 2014;139:822.

    PubMed  PubMed Central  Google Scholar 

  3. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340:115–26.

    Article  CAS  PubMed  Google Scholar 

  4. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Esposito K, Giugliano D. The metabolic syndrome and inflammation: association or causation? Nutr Metab Cardiovasc Dis. 2004;14:228–32.

    Article  CAS  PubMed  Google Scholar 

  6. Schmid-Schönbein GW, Hugli TE. A new hypothesis for microvascular inflammation in shock and multiorgan failure: self-digestion by pancreatic enzymes. Microcirculation. 2005;12:71–82.

    Article  PubMed  Google Scholar 

  7. Khan SS, Singer BD, Vaughan DE. Molecular and physiological manifestations and measurement of aging in humans. Aging Cell. 2017;16:624–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hodes RJ, Sierra F, Austad SN, Epel E, Neigh GN, Erlandson KM, et al. Disease drivers of aging. Ann N Y Acad Sci. 2016;1386:45–68.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15:505–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lee MM, Donahoe PK. Mullerian inhibiting substance: a gonadal hormone with multiple functions. Endocr Rev. 1993;14:152–64.

    CAS  PubMed  Google Scholar 

  11. Taguchi O, Cunha GR, Lawrence WD, Robboy SJ. Timing and irreversibility of Müllerian duct inhibition in the embryonic reproductive tract of the human male. Dev Biol. 1984;106:394–8.

    Article  CAS  PubMed  Google Scholar 

  12. Aksglæde L, Sørensen K, Boas M, Mouritsen A, Hagen C, Jensen RB, et al. Changes in anti-Mullerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab. 2010;95:5357–64.

    Article  PubMed  Google Scholar 

  13. Moolhuijsen LME, Visser JA. Anti-müllerian hormone and ovarian reserve: update on assessing ovarian function. J Clin Endocrinol Metab. 2020;105:3361–73.

    Article  PubMed Central  Google Scholar 

  14. Silva MSB, Giacobini P. New insights into anti-müllerian hormone role in the hypothalamic–pituitary–gonadal axis and neuroendocrine development. Cell Mol Life Sci. 2021;78:1–16.

    Article  CAS  PubMed  Google Scholar 

  15. Qayyum R, Akbar S. Serum anti-mullerian hormone and all-cause mortality in men. Endocrine. 2016;54:225–31.

    Article  CAS  PubMed  Google Scholar 

  16. Olszanecka-Glinianowicz M, Madej P, Owczarek A, Chudek J, Skałba P. Circulating anti‐müllerian hormone levels in relation to nutritional status and selected adipokines levels in polycystic ovary syndrome. Clin Endocrinol. 2015;83:98–104.

    Article  CAS  Google Scholar 

  17. Herawati S. Anti-Mullerian Hormone (AMH) as a novel marker for ovarian function: a review. Bali Medi J. 2019;8:475–81.

    Article  Google Scholar 

  18. Beydoun HA, Hossain S, Beydoun MA, Weiss J, Zonderman AB, Eid SM. Anti-müllerian hormone levels and cardiometabolic disturbances by weight status among men in the 1999 to 2004 national health and nutrition examination survey. J Endocr Soc. 2019;3:921–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ventimiglia E, Capogrosso P, Colicchia M, Boeri L, Serino A, Castagna G, et al. Metabolic syndrome in white E uropean men presenting for primary couple’s infertility: investigation of the clinical and reproductive burden. Andrology. 2016;4:944–51.

    Article  CAS  PubMed  Google Scholar 

  20. Tehrani FR, Erfani H, Cheraghi L, Tohidi M, Azizi F. Lipid profiles and ovarian reserve status: a longitudinal study. Hum Reprod. 2014;29:2522–9.

    Article  CAS  PubMed  Google Scholar 

  21. Sklavos MM, Zhou CK, Pinto LA, Cook MB. Prediagnostic circulating anti-müllerian hormone concentrations are not associated with prostate cancer risk. Cancer Epidemiol Prev Biomarkers. 2014;23:2597–602.

    Article  CAS  Google Scholar 

  22. Dennis NA, Jones GT, Chong YH, van Rij AM, McLennan IS. Serum anti-Mullerian hormone (AMH) levels correlate with infrarenal aortic diameter in healthy older men: is AMH a cardiovascular hormone. J Endocrinol. 2013;219:13–20.

    Article  CAS  PubMed  Google Scholar 

  23. Chong YH, Dennis NA, Connolly MJ, Teh R, Jones GT, van Rij AM, et al. Elderly men have low levels of anti-Müllerian hormone and inhibin B, but with high interpersonal variation: a cross-sectional study of the sertoli cell hormones in 615 community-dwelling men. PloS one. 2013;8:e70967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tzeng C-R, Chang Y-cI, Chang Y-c, Wang C-W, Chen C-H, Hsu M-I. Cluster analysis of cardiovascular and metabolic risk factors in women of reproductive age. Fertil Steril. 2014;101:1404–10.

    Article  PubMed  Google Scholar 

  25. Hoshiya Y, Gupta V, Segev DL, Hoshiya M, Carey JL, Sasur LM, et al. Mullerian inhibiting substance induces NFkB signaling in breast and prostate cancer cells. Mol Cell Endocrinol. 2003;211:43–9.

    Article  CAS  PubMed  Google Scholar 

  26. Lebeurrier N, Launay S, Macrez R, Maubert E, Legros H, Leclerc A, et al. Anti-mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin. J Cell Sci. 2008;121:3357–65.

    Article  CAS  PubMed  Google Scholar 

  27. Ricci M, Mohapatra B, Urbiztondo A, Birusingh RJ, Morgado M, Rodriguez MM, et al. Differential changes in TGF-β/BMP signaling pathway in the right ventricular myocardium of newborns with hypoplastic left heart syndrome. J Card Fail. 2010;16:628–34.

    Article  CAS  PubMed  Google Scholar 

  28. Buyukinan M, Atar M, Pirgon O, Kurku H, Erdem SS, Deniz I. Anti-Mullerian hormone and inhibin B levels in obese boys; relations with cardiovascular risk factors. Exp Clin Endocrinol Diabetes. 2018;126:528–33.

    Article  CAS  PubMed  Google Scholar 

  29. Flurkey KCJ, Harrison DE. Mouse models in aging research. In: Fox JG, Davisson MT, Quimby FW, Barthold SW, Newcomer CE, Smith AL, editors. The mouse in biomedical research. Burlington: Academic Press; 2007. pp. 637–72.

    Chapter  Google Scholar 

  30. Speakman J, Hambly C, Mitchell S, Król E. Animal models of obesity. Obes Rev. 2007;8(Suppl 1):55–61.

    Article  PubMed  Google Scholar 

  31. Kong HS, Kim SK, Lee J, Youm HW, Lee JR, Suh CS, et al. Effect of exogenous anti-müllerian hormone treatment on cryopreserved and transplanted mouse ovaries. Reprod Sci. 2016;23:51–60.

    Article  CAS  PubMed  Google Scholar 

  32. Sriraman V, Niu E, Matias J, Donahoe PK, MacLaughlin DT, Hardy MP, et al. Müllerian inhibiting substance inhibits testosterone synthesis in adult rats. J Androl. 2001;22:750–8.

    CAS  PubMed  Google Scholar 

  33. Clarke T. Mullerian inhibiting substance signaling uses a bone morphogenetic protein (BMP)-like pathway mediated by ALK2 and induces Smad6 expression. Mol Endocrinol. 2001;15:946–59.

    CAS  PubMed  Google Scholar 

  34. Lee YS, Kim JH, Kim ST, Kwon JY, Hong S, Kim SJ, et al. Smad7 and Smad6 bind to discrete regions of Pellino-1 via their MH2 domains to mediate TGF-beta1-induced negative regulation of IL-1R/TLR signaling. Biochem Biophys Res Commun. 2010;393:836–43.

    Article  CAS  PubMed  Google Scholar 

  35. Shalom-Paz E, Weill S, Ginzberg Y, Khatib N, Anabusi S, Klorin G, et al. IUGR induced by maternal chronic inflammation: long-term effect on offspring’s ovaries in rat model-a preliminary report. J Endocrinol Invest. 2017;40:1125–31.

    Article  CAS  PubMed  Google Scholar 

  36. Appt SE, Chen H, Clarkson TB, Kaplan JR. Premenopausal antimullerian hormone concentration is associated with subsequent atherosclerosis. 19. New York: Menopause; 2012. p. 1353.

    Google Scholar 

  37. Kim C, Pan Y, Braffett BH, Arends VL, Steffes MW, Wessells H, et al. Anti-müllerian hormone and its relationships with subclinical cardiovascular disease and renal disease in a longitudinal cohort study of women with type 1 diabetes. Womens Midl Health. 2017;3:5.

    Article  Google Scholar 

  38. de Kat AC, Verschuren WM, Eijkemans MJ, Broekmans FJ, van der Schouw YT. Anti-müllerian hormone trajectories are associated with cardiovascular disease in women: results from the doetinchem cohort study. Circulation. 2017;135:556–65.

    Article  PubMed  Google Scholar 

  39. Looby SE, Fitch KV, Srinivasa S, Lo J, Rafferty D, Martin A, et al. Reduced ovarian reserve relates to monocyte activation and subclinical coronary atherosclerotic plaque in women with HIV. AIDS (London, England). 2016;30:383–93.

    CAS  Google Scholar 

  40. Park HT, Cho GJ, Ahn KH, Shin JH, Kim YT, Hur JY, et al. Association of insulin resistance with anti-Mullerian hormone levels in women without polycystic ovary syndrome (PCOS). Clin Endocrinol. 2010;72:26–31.

    Article  CAS  Google Scholar 

  41. Verit FF, Akyol H, Sakar MN. Low antimullerian hormone levels may be associated with cardiovascular risk markers in women with diminished ovarian reserve. Gynecol Endocrinol. 2016;32:302–5.

    Article  CAS  PubMed  Google Scholar 

  42. Tremellen K, McPhee N, Pearce K. Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men. Basic Clin Androl. 2017;27:5.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31.

    Article  CAS  PubMed  Google Scholar 

  44. Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:1833–42.

    Article  CAS  PubMed  Google Scholar 

  45. Tüttelmann F, Dykstra N, Themmen AP, Visser JA, Nieschlag E, Simoni M. Anti-müllerian hormone in men with normal and reduced sperm concentration and men with maldescended testes. Fertil Steril. 2009;91:1812–9.

    Article  PubMed  Google Scholar 

  46. Håkonsen LB, Thulstrup AM, Aggerholm AS, Olsen J, Bonde JP, Andersen CY, et al. Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men. Reprod Health. 2011;8:24.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Martone AM, Onder G, Vetrano DL, Ortolani E, Tosato M, Marzetti E, et al. Anorexia of aging: a modifiable risk factor for frailty. Nutrients. 2013;5:4126–33.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Pasture Institute of Iran for providing technical support. We also appreciate the cooperation of post-graduate laboratory of Faculty of Nutrition and Food Technology’s management and staff.

Funding

This work was funded by Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences as a doctoral thesis project (Grant No. 1351).

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Authors and Affiliations

  1. Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, PO Box: 19395-4741, Shahrake Qods, Farahzadi, West Arghavan St., Tehran, Iran

    Faezeh Poursoleiman, Hamid Zand, Hadi Monji & Katayoun Pourvali

  2. Department of Physiology and Pharmacology, Pasteur Institute of Iran, PO Box: 1316943551, No. 69, Pasteur Ave, Tehran, Iran

    Hamid Gholami Pourbadie

  3. Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Hadi Monji

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  1. Faezeh Poursoleiman
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Correspondence to Katayoun Pourvali.

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Poursoleiman, F., Zand, H., Pourbadie, H.G. et al. Anti-mullerian hormone attenuates insulin resistance and systemic inflammation in old obese C57BL/6 male mice. J Diabetes Metab Disord 20, 1697–1704 (2021). https://doi.org/10.1007/s40200-021-00925-w

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