Insulin growth factor-1 correlates with higher bone mineral density and lower inflammation status in obese adult subjects

  • Rachele Fornari
  • Chiara Marocco
  • Davide Francomano
  • Simona Fittipaldi
  • Carla Lubrano
  • Viviana M. Bimonte
  • Lorenzo M. Donini
  • Emanuele Nicolai
  • Antonio Aversa
  • Andrea Lenzi
  • Emanuela A. Greco
  • Silvia Migliaccio
Original Article

Abstract

Purpose

Obesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals.

Methods

The study included 426 obese subjects, mean age 44.8 ± 14 years; BMI 34.9 ± 6.1. Exclusion criteria were chronic medical conditions, use of medications affecting bone metabolism, hormonal and nutritional status, recent weight loss, and prior bariatric surgery. Patients underwent measurements of BMD and body composition by DEXA and were evaluated for hormonal, metabolic profile, and inflammatory markers.

Results

In this population, IGF-1 was inversely correlated with abdominal FM% (p < 0.001, r2 = 0.12) and directly correlated with osteocalcin (OSCA) (p < 0.002, r2 = 0.14). A negative correlation was demonstrated between IGF-1 levels and nonspecific inflammatory index, such as fibrinogen (p < 0.01, r2 = 0.04) and erythrocyte sedimentation rate (p < 0.0001, r2 = 0.03). IGF-1 was directly correlated with higher BMD, at both lumbar (p < 0.02, r2 = 0.03) and femoral site (p < 0.04, r2 = 0.03).

Conclusions

In conclusion, our results show that higher levels of serum IGF-1 in obese patients correlate with lower inflammatory pattern and better skeletal health, as demonstrated by higher BMD and osteocalcin levels. These results lead to speculate the existence of a bone-adipose-muscle interplay modulating energy homeostasis, glucose, bone metabolism, and chronic inflammation in individuals affected by abdominal obesity.

Keywords

Obesity Inflammation IGF-1 Bone mineral density 

Notes

Acknowledgements

Research was funded by PRIN 2009 2009KENS9K_004 to LMD, PRIN 2011 052013 to SM, PON 01_00829 to AL, and PRIN 072013. All authors have contributed significantly to the study and are in agreement with the content of the manuscript. All authors: concept/design, collection, and/or assembly of data. FD: data analysis. All authors: interpretation and critical revision of manuscript. All authors: final approval of manuscript.

Compliance with ethical standards

Conflict of interest

SM received speaker’s honorarium from Lilly, Bayer, Italfarmaco, MSD; AA received speaker’s honorarium from Lilly, Bayer. On behalf of all the authors, the corresponding author states that there is no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All subjects provided informed consent before taking part in the study, and the local ethical committee approved the research protocol.

References

  1. 1.
    World Health Organization Technical Report Series (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation 894(i–xii):1–253Google Scholar
  2. 2.
    Migliaccio S, Greco EA, Aversa A et al (2014) Age-associated cardio metabolic diseases and cross-talk between adipose tissue and skeleton: endocrine aspects. Horm Mol Biol Clin Investig 20(1):25–38. doi: 10.1515/hmbci-2014-0030 PubMedGoogle Scholar
  3. 3.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM et al (2010) Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 39:412–423. doi: 10.1093/ageing/afq034 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Brown S, Rosen CJ (2003) Osteoporosis. Med Clin North Am 87:1039–1063CrossRefPubMedGoogle Scholar
  5. 5.
    Zhao LJ, Jiang H, Papasian CJ et al (2008) Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res 23(1):17–29. doi: 10.1359/jbmr.070813 CrossRefPubMedGoogle Scholar
  6. 6.
    Cao JJ (2011) Effects of obesity on bone metabolism. J Orthop Surg Res 6:30. doi: 10.1186/1749-799X-6-30 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Møller N, Jørgensen JO (2009) Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 30:152–177. doi: 10.1210/er.2008-0027 CrossRefPubMedGoogle Scholar
  8. 8.
    Junnila RK, List EO, Berryman DA et al (2013) The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol 9(6):366–376. doi: 10.1038/nrendo.2013.67 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Corpas E, Harman SM, Blackman MR (1993) Human growth hormone and human aging. Endocr Rev 14(1):20–39. doi: 10.1210/edrv-14-1-20 CrossRefPubMedGoogle Scholar
  10. 10.
    Bartke A (2003) Can growth hormone (GH) accelerate aging? Evidence from GH transgenic mice. Neuroendocrinology 78(4):210–216CrossRefPubMedGoogle Scholar
  11. 11.
    Finch CE, Crimmins EM (2004) Inflammatory exposure and historical changes in human life-spans. Science 305(5691):1736–1739. doi: 10.1126/science.1092556 CrossRefPubMedGoogle Scholar
  12. 12.
    Bastard JP, Maachi M, Lagathu C et al (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17(1):4–12PubMedGoogle Scholar
  13. 13.
    Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219–246CrossRefPubMedGoogle Scholar
  14. 14.
    Fornari R, Francomano D, Greco EA et al (2015) Lean mass in obese adult subjects correlates with higher levels of vitamin D, insulin sensitivity and lower inflammation. J Endocrinol Invest 38(3):367–372. doi: 10.1007/s40618-014-0189-z CrossRefPubMedGoogle Scholar
  15. 15.
    Boyd CM, Ritchie CS, Tipton EF et al (2008) From bedside to bench: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Comorbidity and Multiple Morbidity in Older Adults. Aging Clin Exp Res 20(3):181–188CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Franceschi C, Bonafe M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254CrossRefPubMedGoogle Scholar
  17. 17.
    Bruunsgaard H, Pedersen M, Pedersen BK (2001) Aging and proinflammatory cytokines. Curr Opin Hematol 8(3):131–136CrossRefPubMedGoogle Scholar
  18. 18.
    Park MH, Kim DH, Lee EK et al (2014) Age-related inflammation and insulin resistance: a review of their intricate interdependency. Arch Pharm Res 37(12):1507–1514. doi: 10.1007/s12272-014-0474-6 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Pahlavani MA (2004) Influence of caloric restriction on aging immune system. J Nutr Health Aging 8(1):38–47PubMedGoogle Scholar
  20. 20.
    Deepak DDC, Javadpour M, Clark D et al (2010) The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency. Growth Horm IGF Res 20:220–225. doi: 10.1016/j.ghir.2010.02.002 CrossRefPubMedGoogle Scholar
  21. 21.
    Gaspari S, Marcovecchio ML, Breda L et al (2011) Growth in juvenile idiopathic arthritis: the role of inflammation. Clin Exp Rheumatol 29:104–110PubMedGoogle Scholar
  22. 22.
    Berryman DE, List EO, Coschigano KT et al (2004) Comparing adiposity profiles in three mouse models with altered GH signaling. Growth Horm IGF Res 14:309–318. doi: 10.1016/j.ghir.2004.02.005 CrossRefPubMedGoogle Scholar
  23. 23.
    Wang Z, Al-Regaiey KA, Masternak MM et al (2006) Adipocytokines and lipid levels in Ames dwarf and caloric restricted mice. J Gerontol A Biol Sci Med Sci 61A:323–331CrossRefGoogle Scholar
  24. 24.
    Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M et al (2011) Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med 3(70):70ra13. doi: 10.1126/scitranslmed.3001845.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Oliveira JL, Aguiar-Oliveira MH, D’Oliveira A Jr et al (2007) Congenital growth hormone (GH) deficiency and atherosclerosis: effects of GH replacement in GH-naive adults. J Clin Endocrinol Metab 92:4664–4670. doi: 10.1210/jc.2007-1636 CrossRefPubMedGoogle Scholar
  26. 26.
    Baquedano E, Ruiz-Lopez AM, Sustarsic EG et al (2014) The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice. Endocrinology 155(12):4856–4867. doi: 10.1210/en.2014-1367 CrossRefPubMedGoogle Scholar
  27. 27.
    Flier JS (2004) Obesity wars: molecular progress confronts an expanding epidemic. Cell 116:337–350CrossRefPubMedGoogle Scholar
  28. 28.
    Ferrante AW Jr (2007) Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med 262:408–414. doi: 10.1111/j.1365-2796.2007.01852.x CrossRefPubMedGoogle Scholar
  29. 29.
    Andreassen M, Frystyk J, Faber J et al (2012) Growth hormone activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist. Eur J Endocrinol 166:811–819. doi: 10.1530/EJE-11-1009 CrossRefPubMedGoogle Scholar
  30. 30.
    Klein KO, Newfield RS, Hassink SG (2015) Bone maturation along the spectrum from normal weight to obesity: a complex interplay of sex, growth factors and weight gain. J Pediatr Endocrinol Metab. doi: 10.1515/jpem-2015-0234.PubMedGoogle Scholar
  31. 31.
    Terracciano C, Celi M, Lecce D et al (2013) Differential features of muscle fiber atrophy in osteoporosis and osteoarthritis. Osteoporos Int 24:1095–1100. doi: 10.1007/s00198-012-1990-1 CrossRefPubMedGoogle Scholar
  32. 32.
    Lebrasseur NK, Achenbach SJ, Melton LJ 3rd et al (2012) Skeletal muscle mass is associated with bone geometry and microstructure and serum insulin-like growth factor binding protein-2 levels in adult women and men. J Bone Miner Res 27:2159–2169. doi: 10.1002/jbmr0.1666 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Amin S, Riggs BL, Melton LJ 3rd et al (2007) High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. J Bone Miner Res 22:799–807. doi: 10.1359/jbmr.070306 CrossRefPubMedGoogle Scholar
  34. 34.
    Suh HS, Lo Y, Choi N et al (2015) Insulin-like growth factors and related proteins in plasma and cerebrospinal fluids of HIV-positive individuals. J Neuroinflamm 12:72. doi: 10.1186/s12974-015-0288-6 CrossRefGoogle Scholar
  35. 35.
    Ge RT, Mo LH, Wu R et al (2015) Insulin-like growth factor-1 endues monocytes with immune suppressive ability to inhibit inflammation in the intestine. Sci Rep 5:7735. doi: 10.1038/srep07735 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Bredella MA, Gerweck AV, Barber LA et al (2014) Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women. Bone 62:29–35. doi: 10.1016/j.bone.2014.01.022 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Magni P, Dozio E, Galliera E, Ruscica M, Corsi M (2010) Molecular aspects of adipokine–bone interactions. Curr Mol Med 10:522–532PubMedGoogle Scholar
  38. 38.
    Bimonte VM, Fittipaldi S, Marocco C, Emerenziani GP, Fornari R, Guidetti L, Poggiogalle E, Nicolai E, Di Luigi L, Donini LM, Baldari C, Lenzi A, Greco EA, Migliaccio S (2016) Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity. Endocrine. doi: 10.1007/s12020-016-1193-1

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Rachele Fornari
    • 1
  • Chiara Marocco
    • 1
  • Davide Francomano
    • 1
  • Simona Fittipaldi
    • 2
  • Carla Lubrano
    • 1
  • Viviana M. Bimonte
    • 3
  • Lorenzo M. Donini
    • 1
  • Emanuele Nicolai
    • 2
  • Antonio Aversa
    • 4
  • Andrea Lenzi
    • 1
  • Emanuela A. Greco
    • 1
  • Silvia Migliaccio
    • 3
  1. 1.Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and NutritionUniversity “Sapienza”RomeItaly
  2. 2.IRCCS SDNNaplesItaly
  3. 3.Department of Movement, Human and Health Sciences, Section of Health SciencesUniversity “Foro Italico”RomeItaly
  4. 4.Department of Experimental and Clinical MedicineUniversity Magna GraeciaCatanzaroItaly

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