INFORMATIVE NOTE: An opinion on the regulation of bone marrow adipose tissue by dietary fatty acids



Adipose tissue, Bone marrow, Olive oil, Omega-3 PUFAs, Saturated fats


Obesity has a significant impact on predisposition to various diseases and also affects the viabil­ity and choice of haematopoietic stem cells (HSCs) to favour myeloid cell production and/or turnover, all of which are extremely important for the functioning of immune system. As the production of blood cells and mobilization of HSCs and their progeny are regulated, at least in part, by multifaceted interactions through signals that come from the bone marrow (BM) microenvironment, it does not seem astonishing to assume that circumstances that cause alterations in BM structure will unavoidably cause alterations in mesenchymal cells such as adipocytes and lineages from HSCs. The existence of adipose tissue in BM or marrow fat (BMAT) is well known, although its origin, expansion, and functions are poorly understood. Inspired by other studies showing the potential role for olive oil and omega-3 long chain polyunsaturated fatty acids (omega-3 PUFAs) on BM health, and by our own preliminary findings showing the effects of monounsaturated (olive oil) but not saturated (milk cream) dietary fats to contain neutrophils and CD14high monocytes in BM during postprandial periods in healthy volunteers, herein we asked whether dietary fats (saturated fatty acids, SFAs, monounsatu­rated fatty acids, MUFAs, and omega-3 PUFAs) may be a candidate lifestyle factor to modulate the expansion, composition, and function of BMAT, the infiltration of adipose tissue macrophages (ATMs) in BMAT and the mobilization of HSCs and mature myeloid cells from BM during high-fat-induced obesity in mice. This is the first time that the interplay between different dietary fatty acids, obesity, and BM is addressed.


Download data is not yet available.


Abia R, Pacheco YM, Montero E, Ruiz-Gutierrez V, Muriana FJ. 2003. Distribution of fatty acids from dietary oils into phospholipid classes of triacylglycerol-rich lipoproteins in healthy subjects. Life Sciences 72, 1643-1654.

Abia R, Pacheco YM, Perona JS, Montero E, Muriana FJ, Ruiz-Gutierrez V. 2001. The metabolic availability of dietary triacylglycerols from two high oleic oils during the postprandial period does not depend on the amount of oleic acid ingested by healthy men. The Journal of Nutrition 131, 59-65. PMid:11208939

Abia R, Perona JS, Pacheco YM, Montero E, Muriana FJ, Ruiz-Gutierrez V. 1999. Postprandial triacylglycerols from dietary virgin olive oil are selectively cleared in humans. The Journal of Nutrition 129, 2184-2191. PMid:10573547

Adler BJ, Kaushansky K, Rubin CT. 2014. Obesity-driven disruption of haematopoiesis and the bone marrow niche. Nature Reviews. Endocrinology 10, 737-748. PMid:25311396

Bellido C, Lopez-Miranda J, Blanco-Colio LM, Perez-Martinez P, Muriana FJ, Martin-Ventura JL, Marin C, Gomez P, Fuentes F, Egido J, Perez-Jimenez F. 2004. Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor kappaB in peripheral blood mononuclear cells from healthy men. The American Journal of Clinical Nutrition 80, 1487-1491. PMid:15585759

Bermeo S, Vidal C, Zhou H, Duque G. 2015. Lamin A/C acts as an essential factor in mesenchymal stem cell differentia­tion through the regulation of the dynamics of the Wnt/β-catenin pathway. Journal of Cellular Biochemistry 116, 2344-2353. PMid:25846419

Bermudez B, Lopez S, Ortega A, Varela LM, Pacheco YM, Abia R, Muriana FJ. 2011. Oleic acid in olive oil: from a metabolic framework toward a clinical perspective. Current Pharmaceutical Design 17, 831-843. PMid:21443481

Bermudez B, Lopez S, Pacheco YM, Villar J, Muriana FJ, Hoheisel JD, Bauer A, Abia R. 2008. Influence of post­prandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coro­nary artery. Cardiovascular Research 79, 294-303. PMid:18359786

Bermudez B, Lopez S, Varela LM, Ortega A, Pacheco YM, Moreda W, Moreno-Luna R, Abia R, Muriana FJ. 2012. Triglyceride-rich lipoprotein regulates APOB48 receptor gene expression in human THP-1 monocytes and macro­phages. The Journal of Nutrition 142, 227-232. PMid:22190030

Bermudez B, Ortega-Gomez A, Varela LM, Villar J, Abia R, Muriana FJ, Lopez S. 2014. Clustering effects on postpran­dial insulin secretion and sensitivity in response to meals with different fatty acid compositions. Food & Function 5, 1374-1380. PMid:24752559

Boulais PE, Frenette PS. 2015. Making sense of hematopoi­etic stem cell niches. Blood 125, 2621-2629. PMid:25762174 PMCid:PMC4408288

Cawthorn WP, Bree AJ, Yao Y, Du B, Hemati N, Martinez-Santibañez G, MacDougald OA. 2012. Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteo­blastogenesis through a β-catenin-dependent mecha­nism. Bone 50, 477-489. PMid:21872687 PMCid:PMC3261372

Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H, Ning X, Bree AJ, Schell B, Broome DT, Soliman SS, DelProposto JL, Lumeng CN, Mitra A, Pandit SV, Gallagher KA, Miller JD, Krishnan V, Hui SK, Bredella MA, Fazeli PK, Klibanski A, Horowitz MC, Rosen CJ, MacDougald OA. 2014. Bone mar­row adipose tissue is an endocrine organ that contrib­utes to increased circulating adiponectin during caloric restriction. Cell Metabolism 20, 368-375. PMid:24998914 PMCid:PMC4126847

Chen X, Tian HM, Yu XJ. 2012. Bone delivers its energy information to fat and islets through osteocalcin. Orthopaedic Surgery 4, 114-117. PMid:22615158 PMCid:PMC6583110

Cristancho AG, Lazar MA. 2011. Forming functional fat: a growing understanding of adipocyte differentiation. Nature Reviews. Molecular Cell Biology 12, 722-734. PMid:21952300 PMCid:PMC7171550

Devlin MJ, Cloutier AM, Thomas NA, Panus DA, Lotinun S, Pinz I, Baron R, Rosen CJ, Bouxsein ML. 2010. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. Journal of Bone and Mineral Research 25, 2078-2088. PMid:20229598 PMCid:PMC3127399

Eaves CJ. 2015. Hematopoietic stem cells: concepts, definitions, and the new reality. Blood 125, 2605-2613. PMid:25762175 PMCid:PMC4440889

Elbaz A, Wu X, Rivas D, Gimble JM, Duque G. 2010. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro. Journal of Cellular and Molecular Medicine 14, 982-991. PMid:19382912 PMCid:PMC2891630

Fazeli PK, Horowitz MC, MacDougald OA, Scheller EL, Rodeheffer MS, Rosen CJ, Klibanski A. 2013. Marrow fat and bone--new perspectives. The Journal of Clinical Endocrinology and Metabolism 98, 935-945. PMid:23393168 PMCid:PMC3590487

Garcia-Martinez O, Rivas A, Ramos-Torrecillas J, De Luna- Bertos E, Ruiz C. 2014. The effect of olive oil on osteo­porosis prevention. International Journal of Food Sciences and Nutrition 65, 834-840. PMid:24975408

Gasparrini M, Rivas D, Elbaz A, Duque G. 2009. Differential expression of cytokines in subcutaneous and marrow fat of aging C57BL/6J mice. Experimental Gerontology 44, 613-618. PMid:19501151

Geer EB, Shen W, Strohmayer E, Post KD, Freda PU. 2012. Body composition and cardiovascular risk markers after remission of Cushing's disease: a prospective study using whole-body MRI. The Journal of Clinical Endocrinology and Metabolism 97, 1702-1711. PMid:22419708 PMCid:PMC3339890

Gillet C, Spruyt D, Rigutto S, Dalla Valle A, Berlier J, Louis C, Debier C, Gaspard N, Malaisse WJ, Gangji V, Rasschaert J. 2015. Oleate abrogates palmitate-induced lipotoxicity and proinflammatory response in human bone marrow-derived mesenchymal stem cells and osteoblastic cells. Endocrinology 156, 4081-4093. PMid:26327577

Griffith JF, Yeung DK, Ahuja AT, Choy CW, Mei WY, Lam SS, Lam TP, Chen ZY, Leung PC. 2009. A study of bone marrow and subcutaneous fatty acid composition in sub­jects of varying bone mineral density. Bone 44, 1092-1096. PMid:19268721

Gu Y, Filippi MD, Cancelas JA, Siefring JE, Williams EP, Jasti AC, Harris CE, Lee AW, Prabhakar R, Atkinson SJ, Kwiatkowski DJ, Williams DA. 2003. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphos­phatases. Science 302, 445-449. PMid:14564009

Gunaratnam K, Vidal C, Gimble JM, Duque G. 2014. Mechanisms of palmitate-induced lipotoxicity in human osteoblasts. Endocrinology 155, 108-116. PMid:24169557

Hardouin P, Pansini V, Cortet B. 2014. Bone marrow fat. Joint, Bone, Spine 81, 313-319. PMid:24703396

Hayashi K, Yamaguchi T, Yano S, Kanazawa I, Yamauchi M, Yamamoto M, Sugimoto T. 2009. BMP/Wnt antago­nists are upregulated by dexamethasone in osteoblasts and reversed by alendronate and PTH: potential thera­peutic targets for glucocorticoid-induced osteoporosis. Biochemical and Biophysical Research Communications 379, 261-266. PMid:19101512

Kirkland JL, Tchkonia T, Pirtskhalava T, Han J, Karagiannides I. 2002. Adipogenesis and aging: does aging make fat go MAD? Experimental Gerontology 37, 757-767.

Klein G, Schmal O, Aicher WK. 2015. Matrix metalloprotein­ases in stem cell mobilization. Matrix Biology 44, 175-183. PMid:25617493

Kuiperij HB, van Pel M, de Rooij KE, Hoeben RC, Fibbe WE. 2009. Serpina1 (alpha1-AT) is synthesized in the osteoblas­tic stem cell niche. Experimental Hematology 37, 641-647. PMid:19375654

Kurra S, Siris E. 2011. Diabetes and bone health: the relationship between diabetes and osteoporosis-associated fractures. Diabetes Metabolism Research and Reviews 27, 430-435. PMid:21432981

Lapidot T, Dar A, Kollet O. 2005. How do stem cells find their way home? Blood 106, 1901-1910. PMid:15890683

Lau RY, Guo X. 2011. A review on current osteoporosis research: with special focus on disuse bone loss. Journal of Osteoporosis 2011, 293808. PMid:21876833 PMCid:PMC3160709

Lecka-Czernik B. 2006. PPARs and bone metabolism. PPAR Research 2006, 18089. PMid:17259662 PMCid:PMC1679960

Long J, Su YX, Deng HC. 2014. Lipoapoptosis pathways in pan­creatic β-cells and the anti-apoptosis mechanisms of adi­ponectin. Hormone and Metabolic Research 46, 722-727. PMid:25028793

Longo AB, Ward WE. 2016. PUFAs, bone mineral density, and fragility fracture: findings from human studies. Advances in Nutrition 7, 299-312. PMid:26980813 PMCid:PMC4785467

Lopez S, Bermudez B, Abia R, Muriana FJ. 2010. The influ­ence of major dietary fatty acids on insulin secretion and action. Current Opinion in Lipidology 21, 15-20. PMid:19915461

Lopez S, Bermudez B, Montserrat-de la Paz S, Abia R, Muriana FJG. 2018. A microRNA expression signature of the post­prandial state in response to a high-saturated-fat challenge. The Journal of Nutritional Biochemistry 57, 45-55. PMid:29674246

Lopez S, Bermudez B, Ortega A, Varela LM, Pacheco YM, Villar J, Abia R, Muriana FJ. 2011. Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations. The American Journal of Clinical Nutrition 93, 494-499. PMid:21209225

Lopez S, Bermudez B, Pacheco YM, Lopez-Lluch G, Moreda W, Villar J, Abia R, Muriana FJ. 2007. Dietary oleic and palmitic acids modulate the ratio of triacylglycerols to cholesterol in postprandial triacylglycerol-rich lipopro­teins in men and cell viability and cycling in human mono­cytes. The Journal of Nutrition 137, 1999-2005. PMid:17709433

Lopez S, Bermudez B, Pacheco YM, Villar J, Abia R, Muriana FJ. 2008. Distinctive postprandial modulation of beta cell function and insulin sensitivity by dietary fats: monounsat­urated compared with saturated fatty acids. The American Journal of Clinical Nutrition 88, 638-644. PMid:18779278

Lopez S, Jaramillo S, Varela LM, Ortega A, Bermudez B, Abia R, Muriana FJ. 2013. p38 MAPK protects human mono­cytes from postprandial triglyceride-rich lipoprotein-induced toxicity. The Journal of Nutrition 143, 620-626. PMid:23486980

Lopez-Miranda J, Perez-Jimenez F, Ros E, De Caterina R, Badimon L, Covas MI, Escrich E, Ordovas JM, Soriguer F, Abia R, de la Lastra CA, Battino M, Corella D, Chamorro-Quiros J, Delgado-Lista J, Giugliano D, Esposito K, Estruch R, Fernandez-Real JM, Gaforio JJ, La Vecchia C, Lairon D, Lopez-Segura F, Mata P, Menendez JA, Muriana FJ, Osada J, Panagiotakos DB, Paniagua JA, Perez-Martinez P, Perona J, Peinado MA, Pineda-Priego M, Poulsen HE, Quiles JL, Ramirez-Tortosa MC, Ruano J, Serra-Majem L, Sola R, Solanas M, Solfrizzi V, de la Torre-Fornell R, Trichopoulou A, Uceda M, Villalba- Montoro JM, Villar-Ortiz JR, Visioli F, Yiannakouris N. 2008. Olive oil and health: summary of the II interna­tional conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008. Nutrition, Metabolism, and Cardiovascular Diseases 20, 284-294. PMid:20303720

Martin PJ, Haren N, Ghali O, Clabaut A, Chauveau C, Hardouin P, Broux O. 2015. Adipogenic RNAs are transferred in osteoblasts via bone marrow adipocytes-derived extracel­lular vesicles (EVs). BMC Cell Biology 16, 10. PMid:25887582 PMCid:PMC4369894

Massberg S, Schaerli P, Knezevic-Maramica I, Köllnberger M, Tubo N, Moseman EA, Huff IV, Junt T, Wagers AJ, Mazo IB, von Andrian UH. 2007. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 131, 994-1008. PMid:18045540 PMCid:PMC2330270

Mendelson A, Frenette PS. 2014. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nature Medicine 20, 833-846. PMid:25100529 PMCid:PMC4459580

Montserrat-de la Paz S, Bermudez B, Cardelo MP, Lopez S, Abia R, Muriana FJ. 2016. Olive oil and postpran­dial hyperlipidemia: implications for atherosclerosis and metabolic syndrome. Food & Function 7, 4734-4744. PMid:27885367

Morrison SJ, Scadden DT. 2014. The bone marrow niche for haematopoietic stem cells. Nature 505, 327-334. PMid:24429631 PMCid:PMC4514480

Naranjo MC, Garcia I, Bermudez B, Lopez S, Cardelo MP, Abia R, Muriana FJ, Montserrat-de la Paz S. 2016. Acute effects of dietary fatty acids on osteclastogenesis via RANKL/ RANK/OPG system. Molecular Nutrition & Food Research 60, 2505-2513. PMid:27339288

Ng A, Duque G. 2010. Osteoporosis as a lipotoxic disease. IBMS BoneKEy 7, 108-123.

Ortega A, Varela LM, Bermudez B, Lopez S, Abia R, Muriana FJ. 2012. Dietary fatty acids linking postprandial meta­bolic response and chronic diseases. Food & Function 3, 22-27. PMid:22020286

Ortega-Gomez A, Varela LM, Lopez S, Montserrat de la Paz S, Sanchez R, Muriana FJG, Bermudez B, Abia R. 2017. Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor tran­scriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent man­ner. Molecular Nutrition & Food Research 61. PMid:28322000

Pacheco YM, Abia R, Olivera A, Spiegel S, Ruiz-Gutierrez V, Muriana FJ. 2003. Sphingosine 1-phosphate signal sur­vival and mitogenesis are mediated by lipid-stereospe­cific binding of triacylglycerol-rich lipoproteins. Cellular and Molecular Life Sciences 60, 2757-2766. PMid:14685698

Pacheco YM, Abia R, Perona JS, Meier KE, Montero E, Ruiz-Gutierrez V, Muriana FJ. 2002. Triacylglycerol-rich lipoproteins trigger the phosphorylation of extracellular-signal regulated kinases in vascular cells. Life Sciences 71, 1351-1360.

Pacheco YM, Abia R, Perona JS, Reina M, Ruiz-Gutierrez V, Montero E, Muriana FJ. 2001. Triacylglycerol-rich lipo­proteins interact with human vascular cells in a lipid-dependent fashion. Journal of Agricultural and Food Chemistry 49, 5653-5661. PMid:11714373

Pacheco YM, Bermudez B, Lopez S, Abia R, Villar J, Muriana FJ. 2006. Ratio of oleic to palmitic acid is a dietary deter­minant of thrombogenic and fibrinolytic factors during the postprandial state in men. The American Journal of Clinical Nutrition 84, 342-349.

Pacheco YM, Lopez S, Bermudez B, Abia R, Villar J, Muriana FJ. 2008. A meal rich in oleic acid beneficially modulates postprandial sICAM-1 and sVCAM-1 in normoten­sive and hypertensive hypertriglyceridemic subjects. The Journal of Nutritional Biochemistry 19, 200-205. PMid:17651961

Pajerowski JD, Dahl KN, Zhong FL, Sammak PJ, Discher DE. 2007. Physical plasticity of the nucleus in stem cell differ­entiation. Proceedings of the National Academy of Sciences of the United States of America 104, 15619-15624. PMid:17893336 PMCid:PMC2000408

Pittet MJ, Nahrendorf M, Swirski FK. 2014. The journey from stem cell to macrophage. Annals of the New York Academy of Sciences 1319, 1-18. PMid:24673186 PMCid:PMC4074243

Scheller EL, Doucette CR, Learman BS, Cawthorn WP, Khandaker S, Schell B, Wu B, Ding SY, Bredella MA, Fazeli PK, Khoury B, Jepsen KJ, Pilch PF, Klibanski A, Rosen CJ, MacDougald OA. 2015. Region-specific variation in the properties of skeletal adipocytes reveals regulated and con­stitutive marrow adipose tissues. Nature Communications 6, 7808. PMid:26245716 PMCid:PMC4530473

Scheller EL, Rosen CJ. 2014. What's the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health. Annals of the New York Academy of Sciences 1311, 14-30. PMid:24650218 PMCid:PMC4049420

Scheller EL, Troiano N, Vanhoutan JN, Bouxsein MA, Fretz JA, Xi Y, Nelson T, Katz G, Berry R, Church CD, Doucette CR, Rodeheffer MS, Macdougald OA, Rosen CJ, Horowitz MC. 2014. Use of osmium tetroxide stain­ing with microcomputerized tomography to visualize and quantify bone marrow adipose tissue in vivo. Methods in Enzymology 537, 123-139. PMid:24480344 PMCid:PMC4097010

Shen Y, Winkler IG, Barbier V, Sims NA, Hendy J, Levesque JP. 2010. Tissue inhibitor of metalloproteinase-3 (TIMP- 3) regulates hematopoiesis and bone formation in vivo. PLoS One 5, e13086. PMid:20941363 PMCid:PMC2948005

Suchacki KJ, Cawthorn WP, Rosen CJ. 2016. Bone mar­row adipose tissue: formation, function and regulation. Current Opinion in Pharmacology 28, 50-56. PMid:27022859 PMCid:PMC5351553

Taxel P, Kaneko H, Lee SK, Aguila HL, Raisz LG, Lorenzo JA. 2008. Estradiol rapidly inhibits osteoclastogenesis and RANKL expression in bone marrow cultures in postmeno­pausal women: a pilot study. Osteoporosis International 19, 193-199. PMid:17768586

Tian L, Yu X. 2015. Lipid metabolism disorders and bone dys­function--interrelated and mutually regulated (review). Molecular Medicine Reports 12, 783-794. PMid:25760577 PMCid:PMC4438959

Varela LM, Bermudez B, Ortega-Gomez A, Lopez S, Sanchez R, Villar J, Anguille C, Muriana FJ, Roux P, Abia R. 2014. Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signal­ing. Molecular Nutrition & Food Research 58, 1349-1364. PMid:24668798

Varela LM, Lopez S, Ortega-Gomez A, Bermudez B, Buers I, Robenek H, Muriana FJ, Abia R. 2015. Postprandial triglyceride-rich lipoproteins regulate perilipin-2 and per­ilipin-3 lipid-droplet-associated proteins in macrophages. The Journal of Nutritional Biochemistry 26, 327-336. PMid:25595097

Varela LM, Ortega A, Bermudez B, Lopez S, Pacheco YM, Villar J, Abia R, Muriana FJ. 2011. A high-fat meal pro­motes lipid-load and apolipoprotein B-48 receptor tran­scriptional activity in circulating monocytes. The American Journal of Clinical Nutrition 93, 918-925. PMid:21367954

Varela LM, Ortega-Gomez A, Lopez S, Abia R, Muriana FJ, Bermudez B. 2013. The effects of dietary fatty acids on the postprandial triglyceride-rich lipoprotein/apoB48 receptor axis in human monocyte/macrophage cells. The Journal of Nutritional Biochemistry 24, 2031-2039. PMid:24231096

Wang D, Haile A, Jones LC. 2013. Dexamethasone-induced lipolysis increases the adverse effect of adipocytes on osteoblasts using cells derived from human mesenchymal stem cells. Bone 53, 520-530. PMid:23328495

Yu L, Tu Q, Han Q, Zhang L, Sui L, Zheng L, Meng S, Tang Y, Xuan D, Zhang J, Murray D, Shen Q, Cheng J, Kim SH, Dong LQ, Valverde P, Cao X, Chen J. 2015. Adiponectin regulates bone marrow mesenchymal stem cell niche through a unique signal transduction pathway: an approach for treating bone disease in diabetes. Stem Cells 33, 240-252. PMid:25187480 PMCid:PMC4681406

Yuan Z, Li Q, Luo S, Liu Z, Luo D, Zhang B, Zhang D, Rao P, Xiao J. 2016. PPARγ and Wnt signaling in adipogenic and osteogenic differentiation of mesenchymal stem cells. Current Stem Cell Research & Therapy 11, 216-225. PMid:25986621



How to Cite

Lopez S, Lemus-Conejo A, Rosillo MA, Muriana FJ, Abia R. INFORMATIVE NOTE: An opinion on the regulation of bone marrow adipose tissue by dietary fatty acids. Grasas aceites [Internet]. 2020Sep.15 [cited 2024Apr.20];71(3):e362. Available from:




Most read articles by the same author(s)