Fish Oil-Rich Diet Promotes Hematopoiesis and Alters Hematopoietic Niche.

The self-renewal and differentiation of hematopoietic stem cells (HSCs) in bone marrow are essential to replenish all blood cell types, but how this process is influenced by diet remains largely unclear. Here we show that a diet rich in fish oils promotes self-renewal of HSCs and extramedullary hematopoiesis. Chronic intake of a fish oil-rich diet increases the abundance of HSCs, alters the hematopoietic microenvironment, and, intriguingly, induces the expression of matrix metalloproteinase 12 (MMP12) in the bone marrow. Pointing to a direct effect of fish oil on MMP12 expression, omega-3 polyunsaturated fatty acids induce the expression of MMP12 in a dose-dependent manner in bone marrow cells. Importantly, down-regulation of MMP12 activity using an MMP12-specific inhibitor attenuates diet-induced myelopoiesis in both bone marrow and spleen. Thus, a fish oil-rich diet promotes hematopoiesis in the bone marrow and spleen, in part via the activity of MMP12. Taken together, these data provide new insights into diet-mediated regulation of hematopoiesis.

[1]  A. Nagler,et al.  HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver. , 2003, The Journal of clinical investigation.

[2]  J. Lévesque,et al.  Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance , 2012, Nature Medicine.

[3]  Wei Li,et al.  A selective matrix metalloprotease 12 inhibitor for potential treatment of chronic obstructive pulmonary disease (COPD): discovery of (S)-2-(8-(methoxycarbonylamino)dibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408). , 2009, Journal of medicinal chemistry.

[4]  P. Yaqoob.  Fatty acids as gatekeepers of immune cell regulation. , 2003, Trends in immunology.

[5]  D. Jacobs,et al.  Intakes of long-chain omega-3 (n-3) PUFAs and fish in relation to incidence of asthma among American young adults: the CARDIA study. , 2013, The American journal of clinical nutrition.

[6]  K. D. Kikawa,et al.  Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association. , 2010, Carcinogenesis.

[7]  S. Shapiro,et al.  Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. , 1997, Science.

[8]  F. Powrie,et al.  Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation , 2012, Immunity.

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

[10]  R. Visse,et al.  This Review Is Part of a Thematic Series on Matrix Metalloproteinases, Which Includes the following Articles: Matrix Metalloproteinase Inhibition after Myocardial Infarction: a New Approach to Prevent Heart Failure? Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: the Good, the Ba , 2022 .

[11]  K. Nakayama,et al.  Transcriptional up‐regulation of MMPs 12 and 13 by asbestos occurs via a PKCδ‐dependent pathway in murine lung , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  N. Hacohen,et al.  The scavenger receptor SCARF 1 mediates the clearance of apoptotic cells and prevents autoimmunity , 2022 .

[13]  P. Park,et al.  The Lkb1 metabolic sensor maintains haematopoietic stem cell survival , 2010, Nature.

[14]  L. Calvi,et al.  Concise Review: Current Concepts in Bone Marrow Microenvironmental Regulation of Hematopoietic Stem and Progenitor Cells , 2013, Stem cells.

[15]  Ben D. MacArthur,et al.  Mesenchymal and haematopoietic stem cells form a unique bone marrow niche , 2010, Nature.

[16]  H. Ismail.  The role of omega-3 fatty acids in cardiac protection: an overview. , 2005, Frontiers in bioscience : a journal and virtual library.

[17]  Z. Han,et al.  Matrix metalloproteinases in bone marrow : roles of gelatinases in physiological hematopoiesis and hematopoietic malignancies , 2017 .

[18]  E. Passegué,et al.  The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. , 2008, Cell stem cell.

[19]  S. Nilsson,et al.  Bone, microenvironment and hematopoiesis , 2012, Current opinion in hematology.

[20]  Chang H. Kim.  Homeostatic and pathogenic extramedullary hematopoiesis , 2010 .

[21]  V. Sollars,et al.  A High Omega-3 Fatty Acid Diet has Different Effects on Early and Late Stage Myeloid Progenitors , 2010, Lipids.

[22]  Naisyin Wang,et al.  Regulatory activity of polyunsaturated fatty acids in T-cell signaling. , 2010, Progress in lipid research.

[23]  H. Du,et al.  Matrix metalloproteinase 12 overexpression in myeloid lineage cells plays a key role in modulating myelopoiesis, immune suppression, and lung tumorigenesis. , 2011, Blood.

[24]  C. Shaw,et al.  Molecular Signatures of Proliferation and Quiescence in Hematopoietic Stem Cells , 2004, PLoS biology.

[25]  P. Calder.  Immunomodulation by omega-3 fatty acids. , 2007, Prostaglandins, leukotrienes, and essential fatty acids.

[26]  P. Fraker,et al.  Enhancement of hematopoiesis and lymphopoiesis in diet-induced obese mice , 2012 .

[27]  P. Calder,et al.  Fish Oil Supplementation Improves Neutrophil Function During Cancer Chemotherapy , 2012, Lipids.

[28]  T. Ley,et al.  Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Calder,et al.  n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. , 2006, The American journal of clinical nutrition.

[30]  V. Sollars,et al.  Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation , 2009, Lipids in Health and Disease.

[31]  T. Kamijo,et al.  Synergism between stem cell factor and granulocyte-macrophage colony-stimulating factor on cell proliferation by induction of cyclins. , 2002, Cytokine.

[32]  C. Overall,et al.  Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx. , 2008, Blood.

[33]  S. Morrison,et al.  Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells , 2010, Nature.

[34]  M. Lim,et al.  The role of metalloproteinases and their inhibitors in hematological disorders. , 1996, Critical reviews in oncogenesis.

[35]  E. Srour,et al.  Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. , 2010, Blood.

[36]  Xuetao Cao,et al.  Hepatic microenvironment programs hematopoietic progenitor differentiation into regulatory dendritic cells, maintaining liver tolerance. , 2008, Blood.

[37]  A. M. Houghton,et al.  Macrophage elastase kills bacteria within murine macrophages , 2009, Nature.

[38]  A. Kleinfeld,et al.  Membrane partition of fatty acids and inhibition of T cell function. , 1993, Biochemistry.

[39]  T. Mcclanahan,et al.  Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs , 1994, Nature.

[40]  R. Chapkin,et al.  Recent advances in the field of nutritional immunology , 2011, Expert review of clinical immunology.

[41]  G. Kelsoe,et al.  Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow , 2005, The Journal of experimental medicine.

[42]  M. Campieri,et al.  Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. , 1996, The New England journal of medicine.

[43]  S. Rafii,et al.  Recruitment of Stem and Progenitor Cells from the Bone Marrow Niche Requires MMP-9 Mediated Release of Kit-Ligand , 2002, Cell.

[44]  S. Shapiro,et al.  A protean protease: MMP-12 fights viruses as a protease and a transcription factor , 2014, Nature Medicine.

[45]  M. Merad,et al.  Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche , 2011, The Journal of experimental medicine.

[46]  L. Byberg,et al.  Fatty fish in the diet of patients with type 2 diabetes: comparison of the metabolic effects of foods rich in n-3 and n-6 fatty acids. , 2011, The American journal of clinical nutrition.

[47]  J. O’Keefe,et al.  From Inuit to implementation: omega-3 fatty acids come of age. , 2000, Mayo Clinic proceedings.

[48]  S. Armstrong,et al.  FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress , 2007, Cell.

[49]  S. Ostrand-Rosenberg,et al.  Gr-1+ CD11b+ Myeloid-derived Suppressor Cells Suppress Inflammation and Promote Insulin Sensitivity in Obesity* , 2011, The Journal of Biological Chemistry.

[50]  R. Willemze,et al.  Prevention of interleukin-8-induced mobilization of hematopoietic progenitor cells in rhesus monkeys by inhibitory antibodies against the metalloproteinase gelatinase B (MMP-9). , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[51]  A. Franklin,et al.  Membrane raft organization is more sensitive to disruption by (n-3) PUFA than nonraft organization in EL4 and B cells. , 2011, The Journal of nutrition.

[52]  J. Kang,et al.  Endogenous n‐3 fatty acids protect ovariectomy induced bone loss by attenuating osteoclastogenesis , 2009, Journal of cellular and molecular medicine.

[53]  Huaxi Xu,et al.  Chronic intake of high fish oil diet induces myeloid-derived suppressor cells to promote tumor growth , 2014, Cancer Immunology, Immunotherapy.

[54]  D. Scadden,et al.  Evolving concepts on the microenvironmental niche for hematopoietic stem cells , 2008, Current opinion in hematology.

[55]  Irving L. Weissman,et al.  Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells , 2003, Nature.

[56]  I. Morita,et al.  The effects of polyunsaturated fatty acids and their metabolites on osteoclastogenesis in vitro. , 2010, Prostaglandins & other lipid mediators.