Skip to main content

Advertisement

SpringerLink
Log in

Down regulation of the inverse relationship between parathyroid hormone and irisin in male vitamin D-sufficient HIV patients

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Infection with the human immunodeficiency virus (HIV) predisposes to endocrine disorders, manifesting as a metabolic phenotype that affects the entire adipose-musculoskeletal unit (AMS). The present cross-sectional study aimed to investigate differences in irisin and adiponectin concentrations between people living with HIV and healthy controls, as well as to explore potential correlations between the levels of the aforementioned adipokines and markers of calcium homeostasis.

Methods

46 HIV-infected individuals and 39 healthy controls (all men) were included in the study. Anthropometric data, adipokine levels, 25-hydroxyvitamin D [(25(OH)D)] and parathyroid hormone (PTH) concentrations were evaluated in the two groups. Correlations for the relationship between adiponectin, irisin, and PTH levels were examined. The results were adjusted for several confounders, including 25(OH)D levels, anthropometry, physical activity, bone mineral density, testosterone levels, and exposure to ultraviolet B radiation.

Results

Mean adiponectin concentrations were significantly lower in the HIV group compared to the control group: 5868 ± 3668 vs 9068 ± 4277 ng/mL, p = 0.011. The same was applicable to irisin concentrations: 8.31 ± 8.17 (HIV) vs 29.27 ± 27.23 (controls) ng/mL, p = 0.013. A statistically significant and negative correlation was observed between irisin and PTH in the control group (r =  – 0.591; p = 0.033). In contrast, no significant correlation was observed between PTH and irisin in the HIV group (p = 0.898).

Conclusion

Our results are the first to suggest a possible down regulation of the inverse relationship between PTH and irisin in HIV patients and to highlight that AMS dyshomeostasis could be involved in the development of skeletal and adipose HIV-related morbidities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability statement

The data presented in the study are available on reasonable request from the corresponding author.

References

  1. Li F, Li Y, Duan Y, Hu CA, Tang Y, Yin Y (2017) Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue. Cytokine Growth Factor Rev 33:73–82. https://doi.org/10.1016/j.cytogfr.2016.10.003

    Article  CAS  PubMed  Google Scholar 

  2. Chen W, Wang L, You W, Shan T (2021) Myokines mediate the cross talk between skeletal muscle and other organs. J Cell Physiol 236:2393–2412. https://doi.org/10.1002/jcp.30033

    Article  CAS  PubMed  Google Scholar 

  3. Leal LG, Lopes MA, Batista ML Jr (2018) Physical exercise-induced myokines and muscle-adipose tissue crosstalk: a review of current knowledge and the implications for health and metabolic diseases. Front Physiol 9:1307. https://doi.org/10.3389/fphys.2018.01307

    Article  PubMed  PubMed Central  Google Scholar 

  4. Karras SN, Koufakis T, Adamidou L, Dimakopoulos G, Karalazou P, Thisiadou K, Makedou K, Zebekakis P, Kotsa K (2022) Implementation of Christian Orthodox fasting improves plasma adiponectin concentrations compared with time-restricted eating in overweight premenopausal women. Int J Food Sci Nutr 73:210–220. https://doi.org/10.1080/09637486.2021.1941803

    Article  PubMed  Google Scholar 

  5. Krause MP, Milne KJ, Hawke TJ (2019) Adiponectin-consideration for its role in skeletal muscle health. Int J Mol Sci 20:1528. https://doi.org/10.3390/ijms20071528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nawrocki AR, Scherer PE (2004) The delicate balance between fat and muscle: adipokines in metabolic disease and musculoskeletal inflammation. Curr Opin Pharmacol 4:281–289. https://doi.org/10.1016/j.coph.2004.03.003

    Article  CAS  PubMed  Google Scholar 

  7. Waseem R, Shamsi A, Mohammad T, Hassan MI, Kazim SN, Chaudhary AA, Rudayni HA, Al-Zharani M, Ahmad F, Islam A (2022) FNDC5/irisin: physiology and pathophysiology. Molecules 27:1118. https://doi.org/10.3390/molecules27031118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Maak S, Norheim F, Drevon CA, Erickson HP (2021) Progress and challenges in the biology of FNDC5 and Irisin. Endocr Rev 42:436–456. https://doi.org/10.1210/endrev/bnab003

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cho E, Jeong DY, Kim JG, Lee S (2021) The acute effects of swimming exercise on PGC-1α-FNDC5/irisin-UCP1 expression in male C57BL/6J mice. Metabolites 11:111. https://doi.org/10.3390/metabo11020111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Estell EG, Le PT, Vegting Y, Kim H, Wrann C, Bouxsein ML, Nagano K, Baron R, Spiegelman BM, Rosen CJ (2020) Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo. Elife 9:e58172. https://doi.org/10.7554/eLife.58172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kawao N, Kawaguchi M, Ohira T, Ehara H, Mizukami Y, Takafuji Y, Kaji H (2022) Renal failure suppresses muscle irisin expression, and irisin blunts cortical bone loss in mice. J Cachexia Sarcopenia Muscle 13:758–771. https://doi.org/10.1002/jcsm.12892

    Article  PubMed  PubMed Central  Google Scholar 

  12. Luo Y, Ma Y, Qiao X, Zeng R, Cheng R, Nie Y, Li S, Shen X, Yang M, Xu CC, Xu L (2020) Irisin ameliorates bone loss in ovariectomized mice. Climacteric 23:496–504. https://doi.org/10.1080/13697137.2020.1745768

    Article  CAS  PubMed  Google Scholar 

  13. Colaianni G, Cuscito C, Mongelli T, Pignataro P, Buccoliero C, Liu P, Lu P, Sartini L, Di Comite M, Mori G, Di Benedetto A, Brunetti G, Yuen T, Sun L, Reseland JE, Colucci S, New MI, Zaidi M, Cinti S, Grano M (2015) The myokine irisin increases cortical bone mass. Proc Natl Acad Sci U S A 112:12157–12162. https://doi.org/10.1073/pnas.1516622112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Freitas P, Carvalho D, Santos AC, Madureira AJ, Martinez E, Pereira J, Sarmento A, Medina JL (2014) Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome. BMC Infect Dis 14:347. https://doi.org/10.1186/1471-2334-14-347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tsiodras S, Mantzoros C (2006) Leptin and adiponectin in the HIV associated metabolic syndrome: physiologic and therapeutic implications. Am J Infect Dis 2:141–152. https://doi.org/10.3844/ajidsp.2006.141.152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nix LM, Tien PC (2014) Metabolic syndrome, diabetes, and cardiovascular risk in HIV. Curr HIV/AIDS Rep 11:271–278. https://doi.org/10.1007/s11904-014-0219-7

    Article  PubMed  PubMed Central  Google Scholar 

  17. Biver E (2022) Osteoporosis and HIV Infection. Calcif Tissue Int 110:624–640. https://doi.org/10.1007/s00223-022-00946-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Premaor MO, Compston JE (2020) People living with HIV and fracture risk. Osteoporos Int 31:1633–1644. https://doi.org/10.1007/s00198-020-05350-y

    Article  CAS  PubMed  Google Scholar 

  19. Food Processor Analysis Software. 2018. https://www.esha.com/products/food-processor/. Accessed July 2 2022.

  20. Papathanasiou G, Georgoudis G, Papandreou M, Spyropoulos P, Georgakopoulos D, Kalfakakou V, Evangelou A (2009) Reliability measures of the short International Physical Activity Questionnaire (IPAQ) in Greek young adults. Hellenic J Cardiol 50:283–294

    PubMed  Google Scholar 

  21. Mitsionis G, Pakos EE, Stafilas KS, Paschos N, Papakostas T, Beris AE (2009) Normative data on hand grip strength in a Greek adult population. Int Orthop 33:713–717. https://doi.org/10.1007/s00264-008-0551-x

    Article  PubMed  Google Scholar 

  22. Scherzer R, Shen W, Heymsfield SB, Lewis CE, Kotler DP, Punyanitya M, Bacchetti P, Shlipak MG, Grunfeld C (2011) Study of fat redistribution and metabolic change in HIV infection (FRAM). Intermuscular adipose tissue and metabolic associations in HIV infection. Obesity (Silver Spring) 19:283–291. https://doi.org/10.1038/oby.2010.115

    Article  CAS  PubMed  Google Scholar 

  23. Karras SN, Koufakis T, Tsekmekidou X, Antonopoulou V, Zebekakis P, Kotsa K (2020) Increased parathyroid hormone is associated with higher fasting glucose in individuals with normocalcemic primary hyperparathyroidism and prediabetes: a pilot study. Diabetes Res Clin Pract 160:107985. https://doi.org/10.1016/j.diabres.2019.107985

    Article  CAS  PubMed  Google Scholar 

  24. Sajid S, Zariwala MG, Mackenzie R, Turner M, Nell T, Bellary S, Renshaw D (2022) Suppression of anti-inflammatory mediators in metabolic disease may be driven by overwhelming pro-inflammatory drivers. Nutrients 14:2360. https://doi.org/10.3390/nu14112360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wu MV, Bikopoulos G, Hung S, Ceddia RB (2014) Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure. J Biol Chem 289:34129–34140. https://doi.org/10.1074/jbc.M114.591008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rendina-Ruedy E, Rosen CJ (2022) Parathyroid hormone (PTH) regulation of metabolic homeostasis: An old dog teaches us new tricks. Mol Metab. 60:101480. https://doi.org/10.1016/j.molmet.2022.101480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Addy CL, Gavrila A, Tsiodras S, Brodovicz K, Karchmer AW, Mantzoros CS (2003) Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. J Clin Endocrinol Metab 88:627–636. https://doi.org/10.1210/jc.2002-020795

    Article  CAS  PubMed  Google Scholar 

  28. Mynarcik DC, McNurlan MA, Steigbigel RT, Fuhrer J, Gelato MC (2000) Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. J Acquir Immune Defic Syndr 25:312–321. https://doi.org/10.1097/00042560-200012010-00004

    Article  CAS  PubMed  Google Scholar 

  29. Ledru E, Christeff N, Patey O, de Truchis P, Melchior JC, Gougeon ML (2000) Alteration of tumor necrosis factor-alpha T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus-associated lipodystrophy syndrome. Blood 95:3191–3198

    Article  CAS  PubMed  Google Scholar 

  30. Jan V, Cervera P, Maachi M, Baudrimont M, Kim M, Vidal H, Girard PM, Levan P, Rozenbaum W, Lombès A, Capeau J, Bastard JP (2004) Altered fat differentiation and adipocytokine expression are inter-related and linked to morphological changes and insulin resistance in HIV-1-infected lipodystrophic patients. Antivir Ther 9:555–564

    Article  CAS  PubMed  Google Scholar 

  31. Kinlaw WB, Marsh B (2004) Adiponectin and HIV-lipodystrophy: taking HAART. Endocrinology 145:484–486. https://doi.org/10.1210/en.2003-1513

    Article  CAS  PubMed  Google Scholar 

  32. Tong Q, Sankalé JL, Hadigan CM, Tan G, Rosenberg ES, Kanki PJ, Grinspoon SK, Hotamisligil GS (2003) Regulation of adiponectin in human immunodeficiency virus-infected patients: relationship to body composition and metabolic indices. J Clin Endocrinol Metab 88:1559–1564. https://doi.org/10.1210/jc.2002-021600

    Article  CAS  PubMed  Google Scholar 

  33. Vigouroux C, Maachi M, Nguyên TH, Coussieu C, Gharakhanian S, Funahashi T, Matsuzawa Y, Shimomura I, Rozenbaum W, Capeau J, Bastard JP (2003) Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy. AIDS 17:1503–1511. https://doi.org/10.1097/00002030-200307040-00011

    Article  CAS  PubMed  Google Scholar 

  34. Moreno-Perez O, Reyes-Garcia R, Muñoz-Torres M, Merino E, Boix V, Reus S, Giner L, Alfayate R, Garcia-Fontana B, Sanchez-Paya J, Picó A, Portilla J (2018) High Irisin levels in nondiabetic HIV-infected males are associated with insulin resistance, nonalcoholic fatty liver disease, and subclinical atherosclerosis. Clin Endocrinol (Oxf) 89:414–423. https://doi.org/10.1111/cen.13800

    Article  CAS  PubMed  Google Scholar 

  35. Trombeta JCDS, Prestes J, Nascimento DDC, Tibana RA, Pereira GB, Lima TDR, Fraga GA, Vieira-Junior RC, Voltarelli FA (2017) New insights into the effects of irisin levels in HIV-infected subjects: correlation with adiposity, fat-free mass, and strength parameters. Arch Endocrinol Metab 61:382–390. https://doi.org/10.1590/2359-3997000000270

    Article  PubMed  PubMed Central  Google Scholar 

  36. Palermo A, Sanesi L, Colaianni G, Tabacco G, Naciu AM, Cesareo R, Pedone C, Lelli D, Brunetti G, Mori G, Colucci S, Manfrini S, Napoli N, Grano M (2019) A novel interplay between irisin and PTH: from basic studies to clinical evidence in hyperparathyroidism. J Clin Endocrinol Metab 104:3088–3096. https://doi.org/10.1210/jc.2018-02216

    Article  PubMed  Google Scholar 

  37. Anastasilakis AD, Polyzos SA, Makras P, Gkiomisi A, Bisbinas I, Katsarou A, Filippaios A, Mantzoros CS (2014) Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos Int 25:1633–1642. https://doi.org/10.1007/s00198-014-2673-x

    Article  CAS  PubMed  Google Scholar 

  38. He L, He WY, Yang WL, Zhang AH (2018) Lower serum irisin levels are associated with increased vascular calcification in hemodialysis patients. Kidney Blood Press Res 43:287–295. https://doi.org/10.1159/000487689

    Article  CAS  PubMed  Google Scholar 

  39. Colaianni G, Sanesi L, Storlino G, Brunetti G, Colucci S, Grano M (2019) Irisin and bone: from preclinical studies to the evaluation of its circulating levels in different populations of human subjects. Cells 8:451. https://doi.org/10.3390/cells8050451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ahmad IH, Mohamed Mostafa ER, Mohammed SA, Shipl W, Soliman AA, Said M (2023) Correlations between serum testosterone and irisin levels in a sample of Egyptian men with metabolic syndrome; (case-control study). Arch Physiol Biochem 129:180–185. https://doi.org/10.1080/13813455.2020.1808018

    Article  CAS  PubMed  Google Scholar 

  41. Assyov Y, Gateva A, Karamfilova V, Gatev T, Nedeva I, Velikova T, Kamenov ZA (2020) Impact of testosterone treatment on circulating irisin in men with late-onset hypogonadism and metabolic syndrome. Aging Male 23:1381–1387. https://doi.org/10.1080/13685538.2020.1770721

    Article  CAS  PubMed  Google Scholar 

  42. Rochira V, Zirilli L, Orlando G, Santi D, Brigante G, Diazzi C, Carli F, Carani C, Guaraldi G (2011) Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS ONE 6:e28512. https://doi.org/10.1371/journal.pone.0028512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. De Vincentis S, Decaroli MC, Fanelli F, Diazzi C, Mezzullo M, Tartaro G, Tagliavini S, De Santis MC, Roli L, Milic J, Trenti T, Pagotto U, Guaraldi G, Rochira V (2022) Primary, secondary and compensated male biochemical hypogonadism in people living with HIV (PLWH): relevance of sex hormone-binding globulin (SHBG) measurement and comparison between liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay for sex steroids assay. Aging Male 25:41–53. https://doi.org/10.1080/13685538.2022.2039116

    Article  CAS  PubMed  Google Scholar 

  44. De Vincentis S, Decaroli MC, Fanelli F, Diazzi C, Mezzullo M, Morini F, Bertani D, Milic J, Carli F, Cuomo G, Santi D, Tartaro G, Tagliavini S, De Santis MC, Roli L, Trenti T, Pagotto U, Guaraldi G, Rochira V (2021) Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV. Eur J Endocrinol 184:107–122. https://doi.org/10.1530/EJE-20-0855

    Article  PubMed  Google Scholar 

Download references

Funding

No funding was received for conducting this study.

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 1st. Kiriakidi Street, 54636, Thessaloniki, Greece

    S. N. Karras, T. Koufakis, E. Zisimopoulou, P. Mourampetzis, E. Manthou, P. Zebekakis & K. Kotsa

  2. BIOSTATS, Epirus Science and Technology Park Campus of the University of Ioannina, Ioannina, Greece

    G. Dimakopoulos

  3. Laboratory of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece

    P. Karalazou, K. Thisiadou & K. Makedou

  4. Infectious Diseases Division, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece

    O. Tsachouridou, P. Zebekakis & S. Metallidis

Authors
  1. S. N. Karras
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Koufakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Dimakopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Zisimopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Mourampetzis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Manthou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Karalazou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K. Thisiadou
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. O. Tsachouridou
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P. Zebekakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. K. Makedou
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S. Metallidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. K. Kotsa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SNK conceptualized and designed the study. SNK, EZ, PM, EM, PK, KT, KM collected all data. GD performed the statistical analysis. SNK, TK, GD and KK analyzed and interpreted the results. OT, PZ, and SM contributed to the clinical management of the patients involved. SNK, TK, and GD performed the literature review and drafted the first version of the manuscript. All authors have read and critically reviewed the manuscript and approved the final version.

Corresponding author

Correspondence to K. Kotsa.

Ethics declarations

Conflicts of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical standard

Institutional Review Board Statement: The study was carried out according to the Declaration of Helsinki guidelines and was approved by the Institutional Review Board of the AHEPA University Hospital (approval number 25224/2019).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karras, S.N., Koufakis, T., Dimakopoulos, G. et al. Down regulation of the inverse relationship between parathyroid hormone and irisin in male vitamin D-sufficient HIV patients. J Endocrinol Invest 46, 2563–2571 (2023). https://doi.org/10.1007/s40618-023-02112-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-023-02112-5

Keywords

Search

Navigation