Skip to main content
SpringerLink
Log in

An inverted U-shaped relationship between parathyroid hormone and body weight, body mass index, body fat

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

To investigate the relationship between parathyroid hormone (PTH) levels and body weight, body mass index (BMI), lipid profiles, and fat distribution in subjects with primary hyperparathyroidism (PHPT) and controls.

Methods

This was a cross-sectional study in 192 patients with PHPT and 202 controls. Serum concentrations of calcium, 25-hydroxyvitamin D (25(OH)D), PTH, lipids profiles, and other hormones were quantified. Bone mineral density was assessed by dual-energy X-ray absorptiometry. Fat distribution evaluation utilizing quantitative computed tomography was conducted in another 66 patients with PHPT and 155 controls.

Results

PHPT patients were older (P < 0.001) and had less body weight (P < 0.001), lower BMI (P = 0.019), lower serum concentrations of 25(OH)D (P < 0.001), total cholesterol (P = 0.036), low-density lipoprotein-cholesterol (P = 0.036), and higher circulating concentration of free fatty acid (FFA) (P = 0.047) as compared with controls. After adjusting multiple confounders, PTH was positively correlated with weight (r = 0.311, P < 0.001), BMI (r = 0.268, P < 0.01), and visceral adipose tissue area (VAA) (r = 0.191, P < 0.05) in the first tertile of PTH. However, these associations were not observed in the second tertile. While in the third tertile, PTH was negatively correlated with weight (r = –0.200, P < 0.05), BMI (r = –0.223, P < 0.05) and marginally with VAA (r = –0.306, P = 0.065), it showed positive association with FFA (r = 0.230, P < 0.05).

Conclusions

The inverted U-shape relationship between PTH and body weight, BMI, VAA found in this study is helpful to explain the conflicting results among these parameters, and extend our understanding of the metabolic effects of PTH.

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

References

  1. Y. He, R.X. Liu, M.T. Zhu, W.B. Shen, J. Xie, Z.Y. Zhang, N. Chen, C. Shan, X.Z. Guo, Y.D. Lu, B. Tao, L.H. Sun, H.Y. Zhao, R. Guo, B. Li, S.M. Liu, G. Ning, J.Q. Wang, J.M. Liu, The browning of white adipose tissue and body weight loss in primary hyperparathyroidism. EBioMedicine 40, 56–66 (2019)

    Article  PubMed  Google Scholar 

  2. S. Kir, H. Komaba, A.P. Garcia, K.P. Economopoulos, W. Liu, B. Lanske, R.A. Hodin, B.M. Spiegelman., PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer. Cell Metab. 23, 315–323 (2016)

    Article  CAS  PubMed  Google Scholar 

  3. A.B. Grey, M.C. Evans, J.P. Stapleton, I.R. Reid., Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism. Ann. Intern. Med. 121, 745–749 (1994)

    Article  CAS  PubMed  Google Scholar 

  4. M.J. Bolland, A.B. Grey, R.W. Ames, A.M. Horne, G.D. Gamble, I.R. Reid, Fat mass is an important predictor of parathyroid hormone levels in postmenopausal women. Bone 38, 317–321 (2006)

    Article  CAS  PubMed  Google Scholar 

  5. E.O. Billington, G.D. Gamble, I.R. Reid, Parathyroid hormone reflects adiposity and cardiometabolic indices but not bone density in normal men. Bonekey Rep. 5, 852 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. T. Ahlström, E. Hagström, A. Larsson, C. Rudberg, L. Lind, P. Hellman, Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women. Clin. Endocrinol. (Oxf.) 71, 673–678 (2009)

    Article  Google Scholar 

  7. M.J. Bolland, A.B. Grey, G.D. Gamble, I.R. Reid, Association between primary hyperparathyroidism and increased body weight: a meta-analysis. J. Clin. Endocrinol. Metab. 90, 1525–1530 (2005)

    Article  CAS  PubMed  Google Scholar 

  8. C. Cipriani, J. Pepe, B.C. Silva, M.R. Rubin, N.E. Cusano, D.J. McMahon, L. Nieddu, M. Angelozzi, F. Biamonte, D. Diacinti, D. Hans, S. Minisola, J.P. Bilezikian, Comparative effect of rhPTH(1-84) on bone mineral density and trabecular bone score in hypoparathyroidism and postmenopausal osteoporosis. J. Bone Min. Res. 33, 2132–2139 (2018)

    Article  CAS  Google Scholar 

  9. B.C. Silva, J.P. Bilezikian, Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr. Opin. Pharm. 22, 41–50 (2015)

    Article  CAS  Google Scholar 

  10. P. Portillo-Sanchez, F. Bril, R. Lomonaco, D. Barb, B. Orsak, J.M. Bruder, K. Cusi, Effect of pioglitazone on bone mineral density in patients with nonalcoholic steatohepatitis: a 36-month clinical trial. J. Diabetes 11, 223–231 (2019)

    Article  CAS  PubMed  Google Scholar 

  11. K. Engelke, H.K. Genant, J. Griffith. Macroimaging, in J.P. Bilezikian, T.J. Martin, T.L. Clemens, C.J. Rosen (eds). Principles of Bone Biology. 4th edn. (Academic Press, 2020), pp. 1857–1886.

  12. L. Xu, Y. Duanmu, G.M. Blake, C. Zhang, Y. Zhang, K. Brown, X. Wang, P. Wang, X. Zhou, M. Zhang, C. Wang, Z. Guo, G. Guglielmi, X. Cheng, Validation of goose liver fat measurement by QCT and CSE-MRI with biochemical extraction and pathology as reference. Eur. Radio. 28, 2003–2012 (2018)

    Article  Google Scholar 

  13. J.L. Kuk, T.S. Church, S.N. Blair, R. Ross, Does measurement site for visceral and abdominal subcutaneous adipose tissue alter associations with the metabolic syndrome? Diabetes Care 29, 679–684 (2006)

    Article  PubMed  Google Scholar 

  14. J. Wortsman, L.Y. Matsuoka, T.C. Chen, Z. Lu, M.F. Holick, Decreased bioavailability of vitamin D in obesity. Am. J. Clin. Nutr. 72, 690–693 (2000)

    Article  CAS  PubMed  Google Scholar 

  15. S. Corbetta, G. Mantovani, A. Spada, Metabolic syndrome in parathyroid diseases. Front Horm. Res 49, 67–84 (2018)

    Article  CAS  PubMed  Google Scholar 

  16. A.L. Valiña-Tóth, Z. Lai, W. Yoo, A. Abou-Samra, C.A. Gadegbeku, J.M. Flack, Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans. Clin. Endocrinol. (Oxf.) 72, 595–603 (2010)

    Article  Google Scholar 

  17. E. Kamycheva, J. Sundsfjord, R. Jorde, Serum parathyroid hormone level is associated with body mass index. The 5th Tromsø study. Eur. J. Endocrinol. 151, 167–172 (2004)

    Article  CAS  PubMed  Google Scholar 

  18. Z. Ni, M. Smogorzewski, S.G. Massry, Effects of parathyroid hormone on cytosolic calcium of rat adipocytes. Endocrinology 135, 1837–1844 (1994)

    Article  CAS  PubMed  Google Scholar 

  19. M.H. Christensen, S.N. Dankel, Y. Nordbø, J.E. Varhaug, B. Almås, E.A. Lien, G. Mellgren, Primary hyperparathyroidism influences the expression of inflammatory and metabolic genes in adipose tissue. PLoS ONE 6, e20481 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. M.D. Mayas, F.J. Ortega, M. Macías-González, R. Bernal, R. Gómez-Huelgas, J.M. Fernández-Real, F.J. Tinahones, Inverse relation between FASN expression in human adipose tissue and the insulin resistance level. Nutr. Metab. (Lond.) 7, 3 (2010)

    Article  Google Scholar 

  21. L. Koppe, D. Fouque, K. Kalantar-Zadeh, Kidney cachexia or protein-energy wasting in chronic kidney disease: facts and numbers. J. Cachexia Sarcopenia Muscle 10, 479–484 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  22. T. Harsløf, T. Sikjær, L. Sørensen, S.B. Pedersen, L. Mosekilde, B.L. Langdahl, L. Rejnmark, The effect of treatment with PTH on undercarboxylated osteocalcin and energy metabolism in hypoparathyroidism. J. Clin. Endocrinol. Metab. 100, 2758–2762 (2015)

    Article  PubMed  Google Scholar 

  23. A.L. Schafer, D.E. Sellmeyer, A.V. Schwartz, C.J. Rosen, E. Vittinghoff, L. Palermo, J.P. Bilezikian, D.M. Shoback, D.M. Black., Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J. Clin. Endocrinol. Metab. 96, E1982–E1989 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. A. Rastogi, A. Hajela, M. Prakash, N. Khandelwal, R. Kumar, A. Bhattacharya, B.R. Mittal, A. Bhansali, D.G. Armstrong, Teriparatide (recombinant human parathyroid hormone [1-34]) increases foot bone remodeling in diabetic chronic Charcot neuroarthropathy: a randomized double-blind placebo-controlled study. J. Diabetes 11, 703–710 (2019)

    Article  CAS  PubMed  Google Scholar 

  25. S. Kir, J.P. White, S. Kleiner, L. Kazak, P. Cohen, V.E. Baracos, B.M. Spiegelman., Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 513, 100–104 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. O.C. Hedesan, A. Fenzl, A. Digruber, K. Spirk, S. Baumgartner-Parzer, M. Bilban, L. Kenner, M. Vierhapper, A. Elbe-Bürger, F.W. Kiefer., Parathyroid hormone induces a browning program in human white adipocytes. Int J. Obes. (Lond.) 43, 1319–1324 (2019)

    Article  CAS  Google Scholar 

  27. S.E. Ross, N. Hemati, K.A. Longo, C.N. Bennett, P.C. Lucas, R.L. Erickson, O.A. MacDougald., Inhibition of adipogenesis by Wnt signaling. Science 289, 950–953 (2000)

    Article  CAS  PubMed  Google Scholar 

  28. D.H. Balani, H.M. Kronenberg., Withdrawal of parathyroid hormone after prolonged administration leads to adipogenic differentiation of mesenchymal precursors in vivo. Bone 118, 16–19 (2019)

    Article  CAS  PubMed  Google Scholar 

  29. D.J. Rickard, F.L. Wang, A.M. Rodriguez-Rojas, Z. Wu, W.J. Trice, S.J. Hoffman, B. Votta, G.B. Stroup, S. Kumar, M.E. Nuttall., Intermittent treatment with parathyroid hormone (PTH) as well as a non-peptide small molecule agonist of the PTH1 receptor inhibits adipocyte differentiation in human bone marrow stromal cells. Bone 39, 1361–1372 (2006)

    Article  CAS  PubMed  Google Scholar 

  30. B. Jensen, M.C. Farach-Carson, E. Kenaley, K.A. Akanbi, High extracellular calcium attenuates adipogenesis in 3T3-L1 preadipocytes. Exp. Cell Res. 301, 280–292 (2004)

    Article  CAS  PubMed  Google Scholar 

  31. T.T. Huang, M.S. Johnson, R. Figueroa-Colon, J.H. Dwyer, M.I. Goran, Growth of visceral fat, subcutaneous abdominal fat, and total body fat in children. Obes. Res. 9, 283–289 (2001)

    Article  CAS  PubMed  Google Scholar 

  32. A. Misra, N.K. Vikram, Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots. Nutrition 19, 457–466 (2003)

    Article  PubMed  Google Scholar 

  33. M.M. Ibrahim, Subcutaneous and visceral adipose tissue: structural and functional differences. Obes. Rev. 11, 11–18 (2010)

    Article  PubMed  Google Scholar 

  34. M. Ebadi, V.E. Baracos, O.F. Bathe, L.E. Robinson, V.C. Mazurak, Loss of visceral adipose tissue precedes subcutaneous adipose tissue and associates with n-6 fatty acid content. Clin. Nutr. 35, 1347–1353 (2016)

    Article  CAS  PubMed  Google Scholar 

  35. F. Haugen, K.J. Labori, H.J. Noreng, T. Buanes, P.O. Iversen, C.A. Drevon, Altered expression of genes in adipose tissues associated with reduced fat mass in patients with pancreatic cancer. Arch. Physiol. Biochem. 117, 78–87 (2011)

    Article  CAS  PubMed  Google Scholar 

  36. B. Xue, A.G. Greenberg, F.B. Kraemer, M.B. Zemel, Mechanism of intracellular calcium ([Ca2+]i) inhibition of lipolysis in human adipocytes. FASEB J. 15, 2527–2529 (2001)

    Article  CAS  PubMed  Google Scholar 

  37. S. Larsson, H.A. Jones, O. Göransson, E. Degerman, C. Holm, Parathyroid hormone induces adipocyte lipolysis via PKA-mediated phosphorylation of hormone-sensitive lipase. Cell Signal 28, 204–213 (2016)

    Article  CAS  PubMed  Google Scholar 

  38. R. Zechner, F. Madeo, D. Kratky, Cytosolic lipolysis and lipophagy: two sides of the same coin. Nat. Rev. Mol. Cell Biol. 18, 671–684 (2017)

    Article  CAS  PubMed  Google Scholar 

  39. G.F. Lewis, K.D. Uffelman, L.W. Szeto, B. Weller, G. Steiner, Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J. Clin. Invest. 95, 158–166 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. M.D. Jensen, Visceral fat: culprit or canary? Endocrinol. Metab. Clin. North Am. 49, 229–237 (2020)

    Article  PubMed  Google Scholar 

  41. S. Nomura, A. Kitami, R. Takao-Kawabata, A. Takakura, M. Nakatsugawa, R. Kono, A. Maeno, A. Tokuda, Y. Isogai, T. Ishizuya, H. Utsunomiya, M. Nakamura., Teriparatide improves bone and lipid metabolism in a male rat model of type 2 diabetes mellitus. Endocrinology 160, 2339–2352 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Z. Qu, F. Yang, J. Hong, W. Wang, S. Yan, Parathyroid hormone and bone mineral density: a Mendelian randomization study. J. Clin. Endocrinol. Metab. 105, dgaa579 (2020)

    Article  PubMed  Google Scholar 

  43. S.P. Cheng, G.M. Doherty, Y.C. Chang, C.L. Liu., Leptin: the link between overweight and primary hyperparathyroidism? Med. Hypotheses 76, 94–96 (2011)

    Article  CAS  PubMed  Google Scholar 

  44. E. Grethen, K.M. Hill, R. Jones, B.M. Cacucci, C.E. Gupta, A. Acton, R.V. Considine, M. Peacock., Serum leptin, parathyroid hormone, 1,25-dihydroxyvitamin D, fibroblast growth factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity. J. Clin. Endocrinol. Metab. 97, 1655–1662 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. A. Matsunuma, T. Kawane, T. Maeda, S. Hamada, N. Horiuchi, Leptin corrects increased gene expression of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase and -24-hydroxylase in leptin-deficient, ob/ob mice. Endocrinology 145, 1367–1375 (2004)

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (No. 81370018, 81870619, and 81970758).

Author contributions

B.T. and J.-M.L. contributed to the study conception and design. Material preparation, data collection, and analysis were performed by T.-J.Y., L.-P.C., and Y.-L.P. The first draft of the manuscript was written by T.-J.Y., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Author information

Authors and Affiliations

  1. Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai, China

    Tian-Jiao Yuan, Li-Hao Sun, Hong-Yan Zhao, Wei-Qing Wang, Bei Tao & Jian-Min Liu

  2. National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Rui-jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Tian-Jiao Yuan, Li-Hao Sun, Hong-Yan Zhao, Wei-Qing Wang, Bei Tao & Jian-Min Liu

  3. Department of Radiology, Rui-jin Hospital/Lu Wan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Liu-Ping Chen & Yong Lu

  4. Department of Radiology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158 Shang-tang Road, Hangzhou, 310004, Zhejiang, China

    Ya-Ling Pan

Authors
  1. Tian-Jiao Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liu-Ping Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ya-Ling Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Hao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hong-Yan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei-Qing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bei Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jian-Min Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Bei Tao or Jian-Min Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

The study was approved by the Clinical Trail Ethics Committee of Rui-jin hospital, Shanghai Jiao Tong University School of Medicine (2017-201).

Informed consent

Due to the retrospective nature of this study, the ethics committee approved to exempt the written informed consent from participants (2017-201).

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yuan, TJ., Chen, LP., Pan, YL. et al. An inverted U-shaped relationship between parathyroid hormone and body weight, body mass index, body fat. Endocrine 72, 844–851 (2021). https://doi.org/10.1007/s12020-021-02635-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-021-02635-y

Keywords

Search

Navigation