Download PDF
Adipositas - Ursachen, Folgeerkrankungen, Therapie 2019; 13(01): 28-34
DOI: 10.1055/a-0802-0084
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Knochenfett: Pathophysiologische Wechselwirkungen mit dem Metabolischen Syndrom

Bone marrow adipose tissue: pathophysiological interactions with the metabolic syndrome
Tim J. Schulz
1   Abteilung Fettzell-Entwicklung und Ernährung, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
2   Universität Potsdam, Institut für Ernährungswissenschaft, Potsdam-Nuthetal
3   Deutsches Zentrum für Diabetesforschung (DZD), München-Neuherberg
,
Katharina Schmidt-Bleek
4   Julius-Wolff-Institut, Charité Universitätsmedizin, Berlin
5   Berlin Brandenburg Centrum für Regenerative Therapien, Berlin
› Author Affiliations
Further Information

Publication History

Publication Date:
22 February 2019 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Knochenfett stellt ein bisher kaum untersuchtes Fettdepot dar. Diese Population von Fettzellen tritt in den Markhöhlen der meisten Röhrenknochen auf und akkumuliert mit zunehmendem Alter und wird aus diesem Grund seit einiger Zeit mit wichtigen Fehlfunktionen des Knochens im Alter in Zusammenhang gebracht. Aufgrund ihrer besonderen Mikroanatomie innerhalb des Knochens stellt diese Zellpopulation eine spezialisierte Form von Adipozyten dar, die sich zwar morphologisch kaum von den normalen Zellen des restlichen Körperfettes unterscheidet, sich aber in seiner physiologischen Funktion deutlich von ihnen absetzt. Bisherige Studien lassen im gesunden Zustand eine potenzielle regulatorische Rolle vermuten, in der die Fettzellen durch molekulare Interaktionen mit anderen Zelltypen des Knochens, beispielsweise Osteoblasten und hämatopoetischen Zellen, Anteil an der gesunden Knochenhomöostase haben. Unter pathologischen Konditionen, also mit zunehmendem Alter und bei metabolischen Erkrankungen wie Adipositas und Diabetes, verändern sich die molekularen Charakteristika des Knochenfettes zunehmend. Zudem beeinflussen metabolische Konditionen die Bildung von Knochenfett aus mesenchymalen Stammzellen, mitunter zulasten der Entstehung des normalen Knochengewebes, und könnten auf diesem Wege zum Abbau der Knochensubstanz und zur Entwicklung von Osteoporose und erhöhtem Faktur-Risiko beitragen. Zusätzlich beeinflusst Knochenfett den systemischen Energiestoffwechsel und kann durch die Sekretion von Adipokinen in einer Reihe von physiologischen Prozessen eingreifen.

Abstract

Bone marrow adipose tissue is a previously unrecognized depot of fat. Throughout life, this population of adipocytes accumulates in the marrow cavities of long bones and has therefore recently been linked to important aging-related bone disorders. Due to their particular micro-anatomical localization inside the bone, marrow-resident adipocytes represent a specialized type of fat cell that is morphologically almost indistinguishable from regular adipocytes of the other fat depots in the body but is clearly distinct regarding their physiological function. Previous studies have suggested a potential regulatory role in healthy individuals where fat cells influence physiological functions through molecular interactions with other cell types of the bone, such as osteoblasts and hematopoietic cells. Under pathological conditions, including aging and metabolic diseases such as obesity and diabetes, the molecular characteristics of bone marrow fat are increasingly detrimental and may trigger pathophysiological processes in the bone. Metabolic conditions may also influence the formation of bone fat from mesenchymal stem cells, sometimes at the expense of normal bone tissue formation. Metabolic diseases may thus contribute to bone tissue degeneration and the development of osteoporosis and increased fracture risk profiles. Conversely, bone fat affects systemic energy expenditure and regulates a variety of physiological processes through the secretion of adipokines.

Schlüsselwörter

Knochenfett - Osteogenese - Knochenheilung - Adipositas - Metabolisches Syndrom

Key words

Bone marrow adipose tissue - osteogenesis - bone healing - obesity - metabolic syndrome
 

  • Literatur

  • 1 Fazeli PK, Horowitz MC, MacDougald OA. et al. Marrow fat and bone--new perspectives. J Clin Endo Met 2013; 98: 935-945 doi:10.1210/jc.2012–3634
    CrossrefPubMedGoogle Scholar
  • 2 Justesen J, Stenderup K, Ebbesen EN. et al. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontol 2001; 2: 165-171
    CrossrefPubMedGoogle Scholar
  • 3 Griffith JF, Yeung DK, Ma HT. et al. Bone marrow fat content in the elderly: a reversal of sex difference seen in younger subjects. J Magn Reson 2012; 36: 225-230 doi:10.1002/jmri.23619
    CrossrefPubMedGoogle Scholar
  • 4 Kricun ME. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol 1985; 14: 10-19 doi:10.1007/BF00361188
    CrossrefPubMedGoogle Scholar
  • 5 Rosen CJ, Ackert-Bicknell C, Rodriguez JP. et al. Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. Crit Rev Eukaryot Gene Expr 2009; 19: 109-124
    CrossrefPubMedGoogle Scholar
  • 6 Burkhardt R, Kettner G, Bohm W. et al. Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study. Bone 1987; 8: 157-164
    CrossrefPubMedGoogle Scholar
  • 7 Naveiras O, Nardi V, Wenzel PL. et al. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 2009; 460: 259-263 doi:10.1038/nature08099
    PubMedGoogle Scholar
  • 8 Castro JP, Joseph LA, Shin JJ. et al. Differential effect of obesity on bone mineral density in White, Hispanic and African American women: a cross sectional study. Nutr Metab (Lond) 2005; 2: 9 doi:10.1186/1743–7075–2–9
    CrossrefPubMedGoogle Scholar
  • 9 Doucette CR, Horowitz MC, Berry 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 Phys. 2015 DOI: doi:10.1002/jcp.24954 DOI: doi:10.1002/jcp.24954
    CrossrefPubMedGoogle Scholar
  • 10 Douchi T, Yamamoto S, Oki T. et al. Difference in the effect of adiposity on bone density between pre- and postmenopausal women. Maturitas 2000; 34: 261-266
    CrossrefPubMedGoogle Scholar
  • 11 Tavassoli M. Marrow adipose cells. Histochemical identification of labile and stable components. Arch Pathol Lab Med 1976; 100: 16-18
    PubMedGoogle Scholar
  • 12 Scheller EL, Doucette CR, Learman BS. et al. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues. Nature Commun 2015; 6: 7808 doi:10.1038/ncomms8808
    CrossrefPubMedGoogle Scholar
  • 13 Scheller EL, Rosen CJ. What’s the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health. Ann NY Acad Sci 2014; 1311: 14-30 doi:10.1111/nyas.12327
    CrossrefPubMedGoogle Scholar
  • 14 Patsch JM, Li X, Baum T. et al. Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res 2013; 28: 1721-1728 doi:10.1002/jbmr.1950
    CrossrefPubMedGoogle Scholar
  • 15 Yeung DK, Griffith JF, Antonio GE. et al. Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J Magnet Reson 2005; 22: 279-285 doi:10.1002/jmri.20367
    CrossrefPubMedGoogle Scholar
  • 16 Reinke S, Geissler S, Taylor WR. et al. Terminally differentiated CD8(+) T cells negatively affect bone regeneration in humans. Sci Transl Med 2013; 5: 177ra136 doi:10.1126/scitranslmed.3004754
    PubMedGoogle Scholar
  • 17 Schmidt-Bleek K, Schell H, Schulz N. et al. Inflammatory phase of bone healing initiates the regenerative healing cascade. Cell Tissue Res 2012; 347: 567-573 doi:10.1007/s00441–011–1205–7
    CrossrefPubMedGoogle Scholar
  • 18 Ambrosi TH, Scialdone A, Graja A. et al. Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration. Cell Stem Cell. 2017 DOI: doi:10.1016/j.stem.2017.02.009
    CrossrefPubMedGoogle Scholar
  • 19 Chan CKF, Gulati GS, Sinha R. et al. Identification of the Human Skeletal Stem Cell. Cell 2018; 175: 43-56 e21 doi:10.1016/j.cell.2018.07.029
    CrossrefPubMedGoogle Scholar
  • 20 Berry R, Rodeheffer MS. Characterization of the adipocyte cellular lineage in vivo. Nature Cell Biol 2013; 15: 302-308 doi:10.1038/ncb2696
    CrossrefPubMedGoogle Scholar
  • 21 Berendsen AD, Olsen BR. Osteoblast-adipocyte lineage plasticity in tissue development, maintenance and pathology. Cell Mol Life Sci : CMLS 2014; 71: 493-497 doi:10.1007/s00018–013–1440-z
    CrossrefPubMedGoogle Scholar
  • 22 Arner P, Ryden M. The contribution of bone marrow-derived cells to the human adipocyte pool. Adipocyte. 2017 DOI: doi:10.1080/21623945.2017.1306158
    CrossrefPubMedGoogle Scholar
  • 23 Nakashima K, de Crombrugghe B. Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet 2003; 19: 458-466 doi:10.1016/s0168–9525(03)00176–8
    CrossrefPubMedGoogle Scholar
  • 24 Rosen ED, Walkey CJ, Puigserver P. et al. Transcriptional regulation of adipogenesis. Genes Dev 2000; 14: 1293-1307
    PubMedGoogle Scholar
  • 25 Kang S, Akerblad P, Kiviranta R. et al. Regulation of early adipose commitment by Zfp521. PLoS Biol 2012; 10: e1001433 doi:10.1371/journal.pbio.1001433
    CrossrefPubMedGoogle Scholar
  • 26 Addison WN, Fu MM, Yang HX. et al. Direct Transcriptional Repression of Zfp423 by Zfp521 Mediates a Bone Morphogenic Protein-Dependent Osteoblast versus Adipocyte Lineage Commitment Switch. Mol Cell Biol 2014; 34: 3076-3085 doi:10.1128/MCB.00185–14
    CrossrefPubMedGoogle Scholar
  • 27 Ambrosi TH, Schulz TJ. The emerging role of bone marrow adipose tissue in bone health and dysfunction. J Mol Med (Berl) 2017; 95: 1291-1301 doi:10.1007/s00109–017–1604–7
    PubMedGoogle Scholar
  • 28 Schwartz AV, Sellmeyer DE, Vittinghoff E. et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 2006; 91: 3349-3354 doi:10.1210/jc.2005–2226
    CrossrefPubMedGoogle Scholar
  • 29 Pop LM, Lingvay I, Yuan Q. et al. Impact of pioglitazone on bone mineral density and bone marrow fat content. Osteoporos Int. 2017 DOI: doi:10.1007/s00198–017–4164–3
    CrossrefPubMedGoogle Scholar
  • 30 Scheller EL, Cawthorn WP, Burr AA. et al. Marrow Adipose Tissue: Trimming the Fat. Trends Endocrinol Metab. 2016 DOI: doi:10.1016/j.tem.2016.03.016.
    CrossrefPubMedGoogle Scholar
  • 31 Cawthorn WP, Scheller EL, Learman BS. et al. Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab 2014; 20: 368-375 doi:10.1016/j.cmet.2014.06.003
    CrossrefPubMedGoogle Scholar
  • 32 Dietz AA, Steinberg B. Chemistry of bone marrow. VIII. Composition of rabbit bone marrow in inanition. Arch Biochem Biophys 1953; 45: 10-20
    CrossrefPubMedGoogle Scholar
  • 33 Sambuceti G, Brignone M, Marini C. et al. Estimating the whole bone-marrow asset in humans by a computational approach to integrated PET/CT imaging. Eur J Nucl Med Mol Imaging 2012; 39: 1326-1338 doi:10.1007/s00259–012–2141–9
    CrossrefPubMedGoogle Scholar
  • 34 Kajimura D, Lee HW, Riley KJ. et al. Adiponectin regulates bone mass via opposite central and peripheral mechanisms through FoxO1. Cell Metab 2013; 17: 901-915 doi:10.1016/j.cmet.2013.04.009
    CrossrefPubMedGoogle Scholar
  • 35 Laharrague P, Larrouy D, Fontanilles AM. et al. High expression of leptin by human bone marrow adipocytes in primary culture. FASEB J 1998; 12: 747-752
    CrossrefPubMedGoogle Scholar
  • 36 Upadhyay J, Farr OM, Mantzoros CS. The role of leptin in regulating bone metabolism. Metabolism 2015; 64: 105-113 doi:10.1016/j.metabol.2014.10.021
    CrossrefPubMedGoogle Scholar
  • 37 Yue R, Zhou BO, Shimada IS. et al. Leptin Receptor Promotes Adipogenesis and Reduces Osteogenesis by Regulating Mesenchymal Stromal Cells in Adult Bone Marrow. Cell Stem Cell 2016; 18: 1-15 doi:10.1016/j.stem.2016.02.015
    CrossrefPubMedGoogle Scholar
  • 38 Zhou BO, Yu H, Yue R. et al. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF. Nature Cell Biol. 2017 DOI: doi:10.1038/ncb3570 DOI: doi:10.1038/ncb3570
    CrossrefPubMedGoogle Scholar
  • 39 Graef F, Seemann R, Garbe A. et al. Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice. J Musculoskelet Neuronal Interact 2017; 17: 78-85
    PubMedGoogle Scholar
  • 40 Seemann R, Graef F, Garbe A. et al. Leptin-deficiency eradicates the positive effect of traumatic brain injury on bone healing: histological analyses in a combined trauma mouse model. J Musculoskelet Neuronal Interact 2018; 18: 32-41
    PubMedGoogle Scholar
  • 41 Gunaratnam K, Vidal C, Boadle R. et al. Mechanisms of palmitate-induced cell death in human osteoblasts. Biology Open 2013; 2: 1382-1389 doi:10.1242/bio.20136700
    CrossrefPubMedGoogle Scholar
  • 42 Dombrowski S, Kostev K, Jacob L. Use of dipeptidyl peptidase-4 inhibitors and risk of bone fracture in patients with type 2 diabetes in Germany-A retrospective analysis of real-world data. Osteoporos Int. 2017 DOI: doi:10.1007/s00198–017–4051-y
    CrossrefPubMedGoogle Scholar