Exploring the Interplay between Bone Marrow Stem Cells and Obesity

Obesity, a complex disorder with rising global prevalence, is a chronic, inflammatory, and multifactorial disease and it is characterized by excessive adipose tissue accumulation and associated comorbidities. Adipose tissue (AT) is an extremely diverse organ. The composition, structure, and functionality of AT are significantly influenced by characteristics specific to everyone, in addition to the variability connected to various tissue types and its location-related heterogeneity. Recent investigation has shed light on the intricate relationship between bone marrow stem cells and obesity, revealing potential mechanisms that contribute to the development and consequences of this condition. Mesenchymal stem cells within the bone marrow, known for their multipotent differentiation capabilities, play a pivotal role in adipogenesis, the process of fat cell formation. In the context of obesity, alterations in the bone marrow microenvironment may influence the differentiation of mesenchymal stem cells towards adipocytes, impacting overall fat storage and metabolic balance. Moreover, bone marrow’s role as a crucial component of the immune system adds another layer of complexity to the obesity–bone marrow interplay. This narrative review summarizes the current research findings on the connection between bone marrow stem cells and obesity, highlighting the multifaceted roles of bone marrow in adipogenesis and inflammation.

[1]  A. Corsi,et al.  The Impact of Interventional Weight Loss on Bone Marrow Adipose Tissue in People Living with Obesity and Its Connection to Bone Metabolism , 2023, Nutrients.

[2]  Jiayue Hao,et al.  Adipose tissue‑derived extracellular vesicles: Systemic messengers in health and disease (Review) , 2023, Molecular medicine reports.

[3]  L. Grilli,et al.  The Role of BIA Analysis in Osteoporosis Risk Development: Hierarchical Clustering Approach , 2023, Diagnostics.

[4]  K. Alexander,et al.  Sarcopenia and Cardiovascular Diseases , 2023, Circulation.

[5]  Hong-fei Liu,et al.  Obesity and risk of fracture in postmenopausal women: a meta-analysis of cohort studies , 2023, Annals of medicine.

[6]  Qinjian Hao,et al.  Global prevalence of osteosarcopenic obesity amongst middle aged and older adults: a systematic review and meta-analysis , 2023, Archives of Osteoporosis.

[7]  E. Mehraeen,et al.  A systematic review of sarcopenia prevalence and associated factors in people living with human immunodeficiency virus , 2023, Journal of cachexia, sarcopenia and muscle.

[8]  C. Neunaber,et al.  Are the Properties of Bone Marrow-Derived Mesenchymal Stem Cells Influenced by Overweight and Obesity? , 2023, International journal of molecular sciences.

[9]  C. E. Kosmas,et al.  Insulin resistance and cardiovascular disease , 2023, The Journal of international medical research.

[10]  K. Seyssel,et al.  Adipose tissue angiogenesis genes are down-regulated by grape polyphenols supplementation during a human overfeeding trial. , 2023, The Journal of nutritional biochemistry.

[11]  G. Frühbeck,et al.  Contemporary medical, device, and surgical therapies for obesity in adults , 2023, The Lancet.

[12]  C. Porro,et al.  The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line , 2023, International journal of molecular sciences.

[13]  P. Scherer,et al.  Extracellular Matrix (ECM) and Fibrosis in Adipose Tissue: Overview and Perspectives. , 2023, Comprehensive Physiology.

[14]  M. Kassem,et al.  The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity , 2022, Frontiers in Endocrinology.

[15]  Mitsuo Kato,et al.  miR-379 mediates insulin resistance and obesity through impaired angiogenesis and adipogenesis regulated by ER stress , 2022, Molecular therapy. Nucleic acids.

[16]  S. Chieffi,et al.  Physiological Role of Orexinergic System for Health , 2022, International journal of environmental research and public health.

[17]  C. Conte,et al.  Vitamin D in Osteosarcopenic Obesity , 2022, Nutrients.

[18]  J. Body,et al.  Distribution of Fracture Sites in Postmenopausal Overweight and Obese Women: The FRISBEE Study , 2022, Calcified Tissue International.

[19]  Steven M. Romanelli,et al.  Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits , 2022, bioRxiv.

[20]  Jonathan R. Brestoff,et al.  Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue. , 2022, Cell metabolism.

[21]  Y. Lee,et al.  Distinct properties of adipose stem cell subpopulations determine fat depot-specific characteristics. , 2022, Cell metabolism.

[22]  Xiuxiu Huang,et al.  Effect of exercise on bone mineral density among patients with osteoporosis and osteopenia: A systematic review and network meta-analysis. , 2021, Journal of clinical nursing.

[23]  L. Macedo,et al.  Prevalence, incidence, and factors associated with non-specific chronic low back pain in community-dwelling older adults aged 60 years and older: A systematic review and meta-analysis. , 2021, The journal of pain.

[24]  Maya B. Mathur,et al.  Menopausal hormone therapy and women’s health: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials and observational epidemiological studies , 2021, Endocrine Abstracts.

[25]  M. Tarnowski,et al.  Bone Marrow Adipocytes—Role in Physiology and Various Nutritional Conditions in Human and Animal Models , 2021, Nutrients.

[26]  J. Sowers,et al.  Insulin resistance, cardiovascular stiffening and cardiovascular disease. , 2021, Metabolism: clinical and experimental.

[27]  A. Hichami,et al.  Antioxidant and Anti-Inflammatory Potential of Polyphenols Contained in Mediterranean Diet in Obesity: Molecular Mechanisms , 2021, Molecules.

[28]  V. Khanduja,et al.  Pathogenesis and contemporary diagnoses for lateral hip pain: a scoping review , 2020, Knee Surgery, Sports Traumatology, Arthroscopy.

[29]  Natalie C. Ebner,et al.  Innovations in Geroscience to enhance mobility in older adults , 2020, Experimental Gerontology.

[30]  D. Goulis,et al.  Obesity, osteoporosis and bone metabolism , 2020, Journal of musculoskeletal & neuronal interactions.

[31]  M. Tencerova,et al.  Obesity-Induced Changes in Bone Marrow Homeostasis , 2020, Frontiers in Endocrinology.

[32]  M. Manco,et al.  The Bones of Children With Obesity , 2020, Frontiers in Endocrinology.

[33]  V. Gudnason,et al.  Greater Bone Marrow Adiposity Predicts Bone Loss in Older Women , 2020, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  F. Beguinot,et al.  Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes , 2020, Frontiers in Physiology.

[35]  H. Sadie-Van Gijsen The Regulation of Marrow Fat by Vitamin D: Molecular Mechanisms and Clinical Implications , 2019, Current Osteoporosis Reports.

[36]  E. Moriguchi,et al.  Effects of Physical Exercise Programs on Sarcopenia Management, Dynapenia, and Physical Performance in the Elderly: A Systematic Review of Randomized Clinical Trials , 2019, Journal of aging research.

[37]  M. Herrmann Marrow Fat-Secreted Factors as Biomarkers for Osteoporosis , 2019, Current Osteoporosis Reports.

[38]  E. Lespessailles,et al.  Obesity, bariatric surgery and fractures. , 2019, The Journal of clinical endocrinology and metabolism.

[39]  G. de Haan,et al.  Epigenetic Changes as a Target in Aging Haematopoietic Stem Cells and Age-Related Malignancies , 2019, Cells.

[40]  H. Hosokawa,et al.  Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development , 2019, Front. Immunol..

[41]  S. Gilbert,et al.  Obesity in Pediatric Trauma. , 2018, The Orthopedic clinics of North America.

[42]  F. Tang,et al.  TGF-β1 Negatively Regulates the Number and Function of Hematopoietic Stem Cells , 2018, Stem cell reports.

[43]  M. Kassem,et al.  High‐Fat Diet–Induced Obesity Promotes Expansion of Bone Marrow Adipose Tissue and Impairs Skeletal Stem Cell Functions in Mice , 2018, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[44]  M. Bouxsein,et al.  Differential effects of high fat diet and diet-induced obesity on skeletal acquisition in female C57BL/6J vs. FVB/NJ Mice , 2018, Bone reports.

[45]  S. Sauer,et al.  Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone , 2018, Molecular and Cellular Biology.

[46]  A. Viggiano,et al.  Functional Changes Induced by Orexin A and Adiponectin on the Sympathetic/Parasympathetic Balance , 2018, Front. Physiol..

[47]  R. Weiss,et al.  Insulin Resistance, Prediabetes, Metabolic Syndrome: What Should Every Pediatrician Know? , 2017, Journal of clinical research in pediatric endocrinology.

[48]  R. Baron,et al.  Metformin Affects Cortical Bone Mass and Marrow Adiposity in Diet‐Induced Obesity in Male Mice , 2017, Endocrinology.

[49]  C. Rubin,et al.  Exercise Decreases Marrow Adipose Tissue Through ß‐Oxidation in Obese Running Mice , 2017, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[50]  S. Colucci,et al.  Irisin and musculoskeletal health , 2017, Annals of the New York Academy of Sciences.

[51]  D. Tousoulis,et al.  The molecular mechanisms of obesity paradox. , 2017, Cardiovascular research.

[52]  L. Badimón,et al.  Adipose tissue depots and inflammation: effects on plasticity and resident mesenchymal stem cell function. , 2017, Cardiovascular research.

[53]  M. Kassem,et al.  The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis , 2016, Front. Endocrinol..

[54]  K. Kozloff,et al.  Changes in Skeletal Integrity and Marrow Adiposity during High-Fat Diet and after Weight Loss , 2016, Front. Endocrinol..

[55]  R. Eastell,et al.  Free 25-hydroxyvitamin D is low in obesity, but there are no adverse associations with bone health. , 2016, The American journal of clinical nutrition.

[56]  A. Vidal-Puig,et al.  Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues , 2016, Diabetologia.

[57]  X Zhang,et al.  Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? , 2016, Cell Death and Differentiation.

[58]  O. MacDougald,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 , 2015, Journal of cellular physiology.

[59]  B. Lecka-Czernik,et al.  High bone mass in adult mice with diet-induced obesity results from a combination of initial increase in bone mass followed by attenuation in bone formation; implications for high bone mass and decreased bone quality in obesity , 2015, Molecular and Cellular Endocrinology.

[60]  R. Eastell,et al.  Bone Density, Microstructure and Strength in Obese and Normal Weight Men and Women in Younger and Older Adulthood , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[61]  O. MacDougald,et al.  Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. , 2014, Cell metabolism.

[62]  R. Baron,et al.  Direct Transcriptional Repression of Zfp423 by Zfp521 Mediates a Bone Morphogenic Protein-Dependent Osteoblast versus Adipocyte Lineage Commitment Switch , 2014, Molecular and Cellular Biology.

[63]  R. Tuan,et al.  Concise Review: The Surface Markers and Identity of Human Mesenchymal Stem Cells , 2014, Stem cells.

[64]  U. Galderisi,et al.  Sera of overweight people promote in vitro adipocyte differentiation of bone marrow stromal cells , 2014, Stem Cell Research & Therapy.

[65]  A. Ryan,et al.  Intermuscular Fat: A Review of the Consequences and Causes , 2014, International journal of endocrinology.

[66]  M. Bredella,et al.  Ectopic and serum lipid levels are positively associated with bone marrow fat in obesity. , 2013, Radiology.

[67]  Vilmundur Gudnason,et al.  Vertebral bone marrow fat associated with lower trabecular BMD and prevalent vertebral fracture in older adults. , 2013, The Journal of clinical endocrinology and metabolism.

[68]  Binsheng Zhao,et al.  Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study. , 2013, The Journal of clinical endocrinology and metabolism.

[69]  J. Henderson,et al.  Pharmacological inhibition of PPARγ increases osteoblastogenesis and bone mass in male C57BL/6 mice , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[70]  Bernadette A. Thomas,et al.  Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 , 2012, The Lancet.

[71]  N. Crowther,et al.  The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity , 2012, Cellular and Molecular Life Sciences.

[72]  Patrick J. Paddison,et al.  G9a/GLP-dependent histone H3K9me2 patterning during human hematopoietic stem cell lineage commitment. , 2012, Genes & development.

[73]  Heather Ting Ma,et al.  Bone marrow fat content in the elderly: A reversal of sex difference seen in younger subjects , 2012, Journal of magnetic resonance imaging : JMRI.

[74]  R. Müller,et al.  Increased marrow adiposity in premenopausal women with idiopathic osteoporosis. , 2012, The Journal of clinical endocrinology and metabolism.

[75]  M. Gunzer,et al.  Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. , 2012, Cell stem cell.

[76]  A. Schambach,et al.  A Differentiation Checkpoint Limits Hematopoietic Stem Cell Self-Renewal in Response to DNA Damage , 2012, Cell.

[77]  Á. Gil,et al.  Is adipose tissue metabolically different at different sites? , 2011, International journal of pediatric obesity : IJPO : an official journal of the International Association for the Study of Obesity.

[78]  Mami Matsushita,et al.  Age‐Related Decrease in Cold‐Activated Brown Adipose Tissue and Accumulation of Body Fat in Healthy Humans , 2011, Obesity.

[79]  Jay J Cao Effects of obesity on bone metabolism , 2011, Journal of orthopaedic surgery and research.

[80]  Silis Y. Jiang,et al.  Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue. , 2011, American journal of physiology. Regulatory, integrative and comparative physiology.

[81]  Berthold Göttgens,et al.  Transcriptional regulation of haematopoietic transcription factors , 2011, Stem Cell Research & Therapy.

[82]  M. Bredella,et al.  Vertebral Bone Marrow Fat Is Positively Associated With Visceral Fat and Inversely Associated With IGF‐1 in Obese Women , 2011, Obesity.

[83]  T. Bengtsson,et al.  Three years with adult human brown adipose tissue , 2010, Annals of the New York Academy of Sciences.

[84]  M. Marquès,et al.  Adipose Tissue Endothelial Cells From Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence , 2010, Diabetes.

[85]  S. Orkin,et al.  DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells. , 2009, Cell stem cell.

[86]  E. Vellenga,et al.  Repression of BMI1 in normal and leukemic human CD34(+) cells impairs self-renewal and induces apoptosis. , 2009, Blood.

[87]  E. Palmer,et al.  Identification and importance of brown adipose tissue in adult humans. , 2009, The New England journal of medicine.

[88]  G. Duque,et al.  Alendronate Has an Anabolic Effect on Bone Through the Differentiation of Mesenchymal Stem Cells , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[89]  A. Zallone Direct and Indirect Estrogen Actions on Osteoblasts and Osteoclasts , 2006, Annals of the New York Academy of Sciences.

[90]  K. Kotani,et al.  Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle. , 2005, American journal of physiology. Endocrinology and metabolism.

[91]  Ping Chung Leung,et al.  Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy. , 2005, Radiology.

[92]  Mark J. Murphy,et al.  c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. , 2004, Genes & development.

[93]  P. Delmas,et al.  Biochemical Markers of Bone Turnover, Endogenous Hormones and the Risk of Fractures in Postmenopausal Women: The OFELY Study , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[94]  R. Pacifici Editorial: Cytokines, Estrogen, and Postmenopausal Osteoporosis-The Second Decade. , 1998, Endocrinology.

[95]  D. Tenen,et al.  PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony-stimulating factor receptor promoter in myeloid cells. , 1996, Blood.

[96]  D. Tenen,et al.  PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene , 1995, Molecular and cellular biology.

[97]  P. Marie,et al.  Increased proliferation of osteoblast precursor cells in estrogen-deficient rats. , 1993, The American journal of physiology.

[98]  P. Marie,et al.  Osteocalcin and deoxyribonucleic acid synthesis in vitro and histomorphometric indices of bone formation in postmenopausal osteoporosis. , 1989, The Journal of clinical endocrinology and metabolism.

[99]  S. Lord,et al.  Obesity and falls in older people: mediating effects of disease, sedentary behavior, mood, pain and medication use. , 2015, Archives of gerontology and geriatrics.