Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Nutrient regulation of bone marrow adipose tissue: skeletal implications of weight loss

Nature Reviews Endocrinology volume 19, pages 626–638 (2023)Cite this article

Subjects

Abstract

Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis, as well as potentially nourishing the bone marrow during periods of stress. Bone marrow adipose tissue is regulated by multiple factors, but particularly nutrient status. In this Review, we examine how bone marrow adipocytes originate, their function in normal and pathological states and how bone marrow adipose tissue modulates whole-body homoeostasis through actions on bone cells, haematopoietic stem cells and extra-medullary adipocytes during nutritional challenges. We focus on both rodent models and human studies to help understand the unique marrow adipocyte, its response to the external nutrient environment and its effects on the skeleton. We finish by addressing some critical questions that to date remain unanswered.

Key points

  • Adipocytes are critical cellular components of the bone marrow that are regulated by local and systemic factors.

  • Bone marrow adipocytes have unique origins and distinct functions that are distinguishable from extra-medullary adipocytes.

  • In mice and humans, both axial and appendicular bone marrow adipose tissue increase with age and in response to environmental, nutritional and endocrine factors.

  • Both a high-fat diet and caloric restriction enhance the recruitment and differentiation of marrow adipocytes, although their function might differ by nutrient stores.

  • A unique marrow adipocyte-like precursor probably serves as a source of mature bone marrow adipocytes.

  • Increased bone marrow adipose tissue can drive bone loss during high dietary intake or can protect the skeleton during caloric restriction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A timeline of the evolution of our knowledge on bone marrow adipose tissue.
Fig. 2: Skeletal stem cells can differentiate into osteoblasts, chondrocytes, stromal cells or adipocytes.
Fig. 3: Multifunctional marrow adipocytes.

Similar content being viewed by others

References

  1. van de Vyver, M. Immunology of chronic low-grade inflammation: relationship with metabolic function. J. Endocrinol. 257, e220271 (2023).

    PubMed  Google Scholar 

  2. Nicolay, N. H., Lopez Perez, R., Debus, J. & Huber, P. E. Mesenchymal stem cells — a new hope for radiotherapy-induced tissue damage? Cancer Lett. 366, 133–140 (2015).

    Article  CAS  PubMed  Google Scholar 

  3. Nehlin, J. O., Jafari, A., Tencerova, M. & Kassem, M. Aging and lineage allocation changes of bone marrow skeletal (stromal) stem cells. Bone 123, 265–273 (2019).

    Article  PubMed  Google Scholar 

  4. Wang, L. et al. Bone marrow adipocytes: a critical player in the bone marrow microenvironment. Front. Cell Dev. Biol. 9, 770705 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Zhou, W. et al. Ablation of fat cells in adult mice induces massive bone gain. Cell Metab. 32, 801–813.e6 (2020). To our knowledge, the first evidence that marrow adipocytes secrete factors that block osteoblast differentiation.

    Article  Google Scholar 

  6. Zhong et al. Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment. eLife 9, e54695 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Matsushita, Y., Ono, W. & Ono, N. Toward marrow adipocytes: adipogenic trajectory of the bone marrow stromal cell lineage. Front. Endocrinol. 13, 882297 (2022).

    Article  Google Scholar 

  8. Bianco, P. & Robey, P. G. Skeletal stem cells. Development 142, 1023–1027 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Friedenstein, A. J., Chailakhjan, R. K. & Lalykina, K. S. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 3, 393–403 (1970).

    CAS  PubMed  Google Scholar 

  10. Bennet, J. H. et al. Adipocytic cells cultured from marrow have osteogenic potential. J. Cell Sci. 9, 131–139 (1991).

    Article  Google Scholar 

  11. Bianco, P., Robey, P. G. & Simmons, P. J. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2, 313–319 (2008). A classic review paper that defines SSCs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Morikawa et al. Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J. Exp. Med. 206, 2483–2496 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Park, D. et al. Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell 10, 259–272 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jeong, J. H. Adipose stem cells as a clinically available and effective source of adult stem cell therapy. Int. J. Stem Cell 1, 43–48 (2008).

    Article  CAS  Google Scholar 

  15. Guasti, L., New, S. E., Hadjidemetriou, I., Palmiero, M. & Ferretti, P. Plasticity of human adipose-derived stem cells — relevance to tissue repair. Int. J. Dev. Biol. 62, 431–439 (2018).

    Article  CAS  PubMed  Google Scholar 

  16. Gimble, J. M. et al. Adipose-derived stromal/stem cells: a primer. Organogenesis 9, 3–10 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rauch, A. et al. Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis. Nat. Genet. 51, 716–727 (2019).

    Article  CAS  PubMed  Google Scholar 

  18. Ambrosi, T. H. et al. Distinct skeletal stem cell types orchestrate long bone skeletogenesis. eLife 10, e66063 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhou, B. O., Yue, R., Murphy, M. M., Peyer, J. G. & Morrison, S. J. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell 15, 154–168 (2014). A major discovery of the importance of LEPR as a marker of SSCs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Logan, M. et al. Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis 33, 77–80 (2002).

    Article  CAS  PubMed  Google Scholar 

  21. Sanchez-Gurmaches, J., Hsiao, W. Y. & Guertin, D. Highly selective in vivo labeling of subcutaneous white adipocyte precursors with Prx1-Cre. Stem Cell Rep. 4, 541–550 (2015). A critical paper for lineage studies defining Prrx1 as an early marker of mesenchymal progenitors.

    Article  CAS  Google Scholar 

  22. Horowitz, M. C. et al. Bone marrow adipocytes. Adipocytes 6, 193–204 (2017).

    Article  CAS  Google Scholar 

  23. Li, Z. et al. Constitutive bone marrow adipocytes suppress local bone formation. JCI Insight 7, e160915 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  24. He, W. et al. Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proc. Natl Acad. Sci. USA 26, 15712–15717 (2003).

    Article  Google Scholar 

  25. Berry, R. & Rodeheffer, M. S. Characterization of the adipocyte cellular lineage in vivo. Nat. Cell Biol. 15, 302–308 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Naveiras, O. et al. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 460, 259–263 (2009). An important paper adding to the delineation of the marrow adipocyte as a negative regulator of haematopoiesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Greenbaum, A. et al. CXCL12 production by early mesenchymal progenitors is required for hematopoietic stem cell maintenance. Nature 495, 227–230 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mizoguchi, T. et al. Osterix marks distinct waves of primitive and definitive stroma; progenitors during bone marrow development. Dev. Cell 29, 340–349 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu, Y. et al. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma. PLoS ONE 8, e71318 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ambrosi, T. H. et al. Adipocyte accumulation in bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell 20, 771–784 (2017). An important paper to show the effect of marrow adipocytes on haematopoietic and skeletal progenitors with ageing.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chan, C. K. F. et al. Identification and specification of the mouse skeletal stem. Cell 160, 285–298 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shao, M. et al. Zfp423 maintains white adipocyte identity through suppression of the beige cell thermogenic gene program. Cell Metab. 23, 1167–1184 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chandra, A. et al. Suppression of sclerostin alleviates radiation-induced bone loss by protecting bone-forming cells and their progenitors through distinct mechanisms. J. Bone Miner. Res. 32, 360–372 (2017).

    Article  CAS  PubMed  Google Scholar 

  34. Vieira, R. et al. Sugar-lowering drugs for type 2 diabetes mellitus and metabolic syndrome — review of classical and new compounds: part-I. Pharmaceuticals 12, 152 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Worthley, D. L. et al. Gremlin 1 identifies a skeletal stem cell with bone cartilage, and reticular stromal potential. Cell 160, 269–284 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Scheller, E. L. et al. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues. Nat. Commun. 6, 7808 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Boyd, A. L. et al. Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche. Nat. Cell Biol. 19, 1336–1347 (2017).

    Article  CAS  PubMed  Google Scholar 

  38. Boroumand, P. et al. Bone marrow adipocytes drive the development of tissue invasive Ly6C high monocytes during obesity. eLife 11, e65553 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Zhong, L. et al. Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone. eLife 12, e82112 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Galic, S., Oakhill, J. S. & Steinberg, G. R. Adipose tissue as an endocrine organ. Mol. Cell. Endocrinol. 316, 129–139 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Sun, K., Kusminski, C. M. & Scherer, P. E. Adipose tissue remodeling and obesity. J. Clin. Invest. 121, 2094–2101 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tavassoli, M., Eastlund, D. T., Yam, L. T., Neiman, R. S. & Finkel, H. Gelatinous transformation of bone marrow in prolonged self-induced starvation. Scand. J. Haematol. 16, 311–319 (1976).

    PubMed  Google Scholar 

  43. Devlin, M. J. Why does starvation make bones fat? Am. J. Hum. Biol. 23, 577–85 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Animal Disease Diagnostic Laboratory: Purdue University. Bone marrow fat analysis as a measure of starvation in animals. Animal Disease Diagnostic Laboratory https://www.addl.purdue.edu/newsletters/2006/Winter/bmfa.htm (2006).

  45. Bermudez, B., Ishii, T., Wu, Y. H., Carpenter, R. D. & Sherk, V. D. Energy balance and bone health: a nutrient availability perspective. Curr. Osteoporos. Rep. 21, 77–84 (2023).

    Article  PubMed  Google Scholar 

  46. Ali, D. et al. High-fat diet-induced obesity augments the deleterious effects of estrogen deficiency on bone: evidence from ovariectomized mice. Aging Cell 12, e13726 (2022).

    Article  Google Scholar 

  47. Tencerova, M. et al. High-fat diet-induced obesity promotes expansion of bone marrow adipose tissue and impairs skeletal stem cell functions in mice. J. Bone Min. Res. 6, 1154–1165 (2018). One of the important studies tying obesity to marrow adiposity.

    Article  Google Scholar 

  48. Dimitri, P., Bishop, N., Walsh, J. S. & Eastell, R. Obesity is a risk factor for fracture in children but is protective against fracture in adults: a paradox. Bone 50, 457–466 (2012).

    Article  CAS  PubMed  Google Scholar 

  49. Rosen, C. J. & Bouxsein, M. L. Mechanisms of disease: is osteoporosis the obesity of bone? Nat. Clin. Pract. Rheumatol. 2, 35–43 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. de Araujo, I. M. et al. Marrow adipose tissue spectrum in obesity and type 2 diabetes mellitus. Eur. J. Endocrinol. 176, 21–30 (2017).

    Article  PubMed  Google Scholar 

  51. Villareal, D. T. et al. Effect of two-year caloric restriction on bone metabolism and bone mineral density in non-obese younger adults: a randomized clinical trial. J. Bone Min. Res. 31, 40–51 (2016). A classic paper showing that caloric restriction improves surrogates of cardiovascular health but causes bone loss.

    Article  CAS  Google Scholar 

  52. Zibellini, J. et al. Does diet-induced weight loss lead to bone loss in overweight or obese adults? A systematic review and meta-analysis of clinical trials. J. Bone Min. Res. 30, 2168–2178 (2015).

    Article  CAS  Google Scholar 

  53. Hadi, Y. B. et al. Metabolic bone disease and fracture risk after gastric bypass and sleeve gastrectomy: comparative analysis of a multi-institutional research network. Surg. Obes. Relat. Dis. 18, 604–609 (2022).

    Article  PubMed  Google Scholar 

  54. Fazeli, P. K. et al. The dynamics of human bone marrow adipose tissue in response to feeding and fasting. JCI Insight 6, e138636 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Holanda, N. et al. Musculoskeletal effects of obesity and bariatric surgery — a narrative review. Arch. Endocrinol. Metab. 66, 621–632 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Doucette, C. R. et al. A high fat diet increases bone marrow adipose tissue (MAT) but does not alter trabecular or cortical bone mass in C57BL/6J mice. J. Cell. Physiol. 230, 2032–2037 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Devlin, M. J. et al. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. J. Bone Miner. Res. 25, 2078–2088 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Li, Z. et al. G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche. J. Clin. Invest. 129, 2404–2416 (2019). One of the mechanisms of gastric-bypass-induced bone loss is mediated through G-CSF.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Bornstein, S. et al. FGF-21 and skeletal remodeling during and after lactation in C57BL/6J. Endocrinology 155, 3516–3526 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Bachmann, K. N. et al. Vertebral volumetric bone density and strength are impaired in women with low-weight and atypical anorexia nervosa. J. Clin. Endocrinol. Metab. 102, 57–68 (2017).

    PubMed  Google Scholar 

  61. Cawthorn, W. P. et al. Expansion of bone marrow adipose tissue during caloric restriction is associated with increased circulating glucocorticoids and not with hypoleptinemia. Endocrinology 157, 508–521 (2016).

    Article  CAS  PubMed  Google Scholar 

  62. Fazeli, P. K. et al. Preadipocyte factor-1 is associated with marrow adiposity and bone mineral density in women with anorexia nervosa. J. Clin. Endocrinol. Metab. 95, 407–413 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Milos, G. et al. Positive effect of teriparatide on areal bone mineral density in young women with anorexia nervosa: a pilot study. Calcif. Tissue Int. 108, 595–604 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Fazeli, P. K. et al. Teriparatide increases bone formation and bone mineral density in adult women with anorexia nervosa. J. Clin. Endocrinol. Metab. 99, 1322–1329 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Colling, C. et al. Changes in serum cortisol 10 days after overfeeding or fasting. Am. J. Physiol. Endocrinol. Metab. 324, E506–E513 (2023).

    Article  CAS  PubMed  Google Scholar 

  66. Fan, Y. et al. PTH directs bone marrow mesenchymal cell fate. Cell Metab. 25, 661–672 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zhong, L. et al. Transient expansion and myofibroblast conversion of adipogenic lineage precursors mediate bone marrow repair after radiation. JCI Insight 7, e150323 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Piotrowska, K. & Tarnowski, M. Bone marrow adipocytes — role in physiology and various nutritional conditions in human and animal models. Nutrients 13, 1412 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Reitman, M. L. & Gavrilova, O. A-ZIP/F-1 mice lacking white fat: a model for understanding lipoatrophic diabetes. Int. J. Obes. Relat. Metab. Disord. 24, S11–S14 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Zhou, B. O. et al. Bone marrow adipocytes promote the regeneration of stem cells and hematopoiesis by secreting SCF. Nat. Cell Biol. 19, 891–903 (2017). A critical paper that delineates how bone marrow adipocytes might enhance haematopoiesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Qiu, W. et al. Patients with high bone mass phenotype exhibit enhanced osteoblast differentiation and inhibition of adipogenesis of human mesenchymal stem cells. J. Bone Min. Res. 22, 1720–1731 (2007).

    Article  CAS  Google Scholar 

  72. Li, Z. et al. Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits. eLife 11, e78496 (2022). A seminal paper that defines how, during caloric restriction, regulated marrow adipose tissue might protect the skeleton.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ables, G. P. & Johnson, J. E. Pleiotropic responses to methionine restriction. Exp. Gerontol. 94, 83–88 (2017).

    Article  CAS  PubMed  Google Scholar 

  74. Plummer, J., Park, M., Perodin, F., Horowitz, M. C. & Hens, J. R. Methionine-restricted diet increases miRNAs that can target RUNX2 expression and alters bone structure in young mice. J. Cell. Biochem. 118, 31–42 (2017).

    Article  CAS  PubMed  Google Scholar 

  75. Ouattara, A., Cooke, D., Gopalakrishnan, R., Huang, T.-H. & Ables, G. P. Methionine restriction alters bone morphology and affects osteoblast differentiation. Bone Rep. 5, 33–42 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Richie, J. P. et al. Dietary methionine and total sulfur amino acid restriction in healthy adults. J. Nutr. Health Aging 27, 111–123 (2023).

    PubMed  Google Scholar 

  77. Meunier, P., Aaron, J., Edouard, C. & Vignon, G. Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin. Orthop. Relat. Res. 80, 147–154 (1971). To our knowledge, the first description of the relationship between marrow adipose tissue and bone.

    Article  CAS  PubMed  Google Scholar 

  78. Yeung, D. K. et al. Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J. Magn. Reson. Imaging 22, 279–285 (2005).

    Article  PubMed  Google Scholar 

  79. Shen, W. et al. MRI-measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women. Osteoporos. Int. 18, 641–647 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Syed, F. A. et al. Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women. Osteoporos. Int. 19, 1323–1330 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Aron, N. et al. Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells. eLife 10, e69209 (2021).

    Article  Google Scholar 

  82. Emont, M. P. et al. A single-cell atlas of human and mouse white adipose tissue. Nature 603, 926–933 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Rosen, C. J. Extensive expertise in endocrinology. My quarter century quest to understand the paradox of marrow adiposity. Eur. J. Endocrinol. 187, R17–R26 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Maridas, D. E., DeMambro, V. E., Le, P., Mohan, S. & Rosen, C. J. IGFBP-4 is required for adipogenesis and adipose distribution. Endocrinology 158, 3488–3500 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zou, Q. et al. Risk of fracture following gastric surgery for benign and malignant conditions: a study level pooled analysis of population-based cohort studies. Front. Oncol. 12, 1001662 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Aaseth, J. O. & Alexander, J. Postoperative osteoporosis in subjects with morbid obesity undergoing bariatric surgery with gastric bypass or sleeve gastrectomy. Nutrients 15, 1302 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sanchez-Gurmaches, J. & Guertin, D. A. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat. Commun. 5, 4099 (2014).

    Article  CAS  PubMed  Google Scholar 

  88. Chapman, J. & Vega, F. Incidental brown adipose tissue in bone marrow biopsy. Blood 130, 952 (2017).

    Article  CAS  PubMed  Google Scholar 

  89. Dannheim, K. & Bhargava, P. A rare finding of brown fat in bone marrow as a mimic for metastatic disease. Am. J. Hematol. 91, 545–546 (2016).

    Article  PubMed  Google Scholar 

  90. Rahman, S. et al. Inducible brown adipose tissue, or beige fat, is anabolic for the skeleton. Endocrinology 154, 2687–2701 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Krings, A. et al. Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone 50, 546–552 (2012).

    Article  CAS  PubMed  Google Scholar 

  92. Scheller, E. L. et al. Use of osmium tetroxide staining with microcomputerized tomography to visualize and quantify bone marrow adipose tissue in vivo. Meth. Enzymol. 537, 123–139 (2014).

    Article  CAS  Google Scholar 

  93. Cannon, B. & Nedergaard, J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84, 277–359 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Craft, C. S. et al. Bone marrow adipose tissue does not express UCP1 during development or adrenergic-induced remodeling. Sci. Rep. 9, 17427 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Thompson J. C., Carvalho S., Marean C. W. & Alemseged, Z., Origins of the human predatory pattern: the transition to large-animals exploitation by early hominins. Curr. Anthropol. https://doi.org/10.1086/701477 (2019).

  96. Plummer, T. W. et al. Expanded geographic distribution and dietary strategies of the earliest Oldoman hominins and Paranthropus. Science 379, 561–566 (2023).

    Article  CAS  PubMed  Google Scholar 

  97. Steele R. Hygenic Physiology: Skin and Bone (1883).

  98. Feussner, J. R., Shelburne, J. D., Bredehoeft, S. & Cohen, H. J. Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis. Blood 53, 820–827 (1979).

    Article  CAS  PubMed  Google Scholar 

  99. Tavassoli, M. & Crosby, W. H. Bone marrow histogenesis: a comparison of fatty and red marrow. Science 169, 291–293 (1970). To our knowledge, the first characterization of marrow adipocytes and their relationship to bone marrow haematopoiesis.

    Article  CAS  PubMed  Google Scholar 

  100. Feng, C. S. Gelatinous transformation of marrow in a case of acute myelogenous leukemia post-chemotherapy. Am. J. Hematol. 38, 220–222 (1991).

    Article  CAS  PubMed  Google Scholar 

  101. Bredella, M. A. et al. Increased bone marrow fat in anorexia nervosa. J. Clin. Endocrinol. Metab. 94, 2129–2136 (2009). The paradoxical increase in marrow adipose tissue with peripheral adipose tissue loss drove the field of nutrition, endocrinology and bone biology.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Gao, Y. et al. Magnetic resonance imaging-measured bone marrow adipose tissue area is inversely related to cortical bone area in children and adolescents aged 5–18 years. J. Clin. Densitom. 18, 203–208 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Griffith, J. F., Yeung, D. K., Chow, S. K., Leung, J. C. & Leung, P. C. Reproducibility of MR perfusion and 1H spectroscopy of bone marrow. J. Magn. Reson. Imaging 29, 1438–1442 (2009).

    Article  PubMed  Google Scholar 

  104. Tencerova, M. et al. Obesity-associated hypermetabolism and accelerated senescence of bone marrow stromal stem cells suggest a potential mechanism for bone fragility. Cell Rep. 27, 2050–2062 (2019).

    Article  CAS  PubMed  Google Scholar 

  105. Akune, T. et al. PPARγ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J. Clin. Invest. 113, 846–855 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Velickovic, K. et al. Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro. Sci. Rep. 8, 4974 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Balani, D. H. & Kronenbergy, H. M. Withdrawal of parathyroid hormone after prolonged administration leads to adipogenic differentiation of mesenchymal precursors in vivo. Bone 118, 16–19 (2019). A classic paper demonstrating the effect of PTH on skeletal progenitor lineage.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support of National Institute of Diabetes and Digestive and Kidney Diseases R24 092759-09.

Author information

Authors and Affiliations

  1. Maine Health Institute for Research, Scarborough, ME, USA

    Clifford J. Rosen

  2. Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA

    Mark C. Horowitz

Authors
  1. Clifford J. Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark C. Horowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of this Review.

Corresponding authors

Correspondence to Clifford J. Rosen or Mark C. Horowitz.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Endocrinology thanks Frederic Deschaseaux, Moustapha Kassem and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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

Rosen, C.J., Horowitz, M.C. Nutrient regulation of bone marrow adipose tissue: skeletal implications of weight loss. Nat Rev Endocrinol 19, 626–638 (2023). https://doi.org/10.1038/s41574-023-00879-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-023-00879-4

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing