Long-chain polyunsaturated fatty acids may mutually benefit both obesity and osteoporosis

Nutrition Research

Volumn 33, Issue 7, 2013, Pages 521-533

  Kelly, Owen J ^a   Gilman, Jennifer C ^b   Kim, Youjin ^c   Ilich, Jasminka Z ^d  

^a ABBOTT LABORATORIES   (United States)

^b TEXAS WOMAN'S UNIVERSITY   (United States)

^c BAYER AG   (Germany)

^d FLORIDA STATE UNIVERSITY   (United States)

Author keywords

Inflammation; Mesenchymal stem cells; Obesity; Omega 3 fatty acids; Osteoporosis

Indexed keywords

C REACTIVE PROTEIN; DOCOSAHEXAENOIC ACID; ESTROGEN; ICOSAPENTAENOIC ACID; INTERLEUKIN 6; LEPTIN; LONG CHAIN FATTY ACID; OMEGA 3 FATTY ACID; OMEGA 6 FATTY ACID; OSTEOCALCIN; POLYUNSATURATED FATTY ACID;

ADIPOGENESIS; ANTIINFLAMMATORY ACTIVITY; BARIATRIC SURGERY; BONE DENSITY; BONE DEVELOPMENT; BONE MASS; BONE METABOLISM; BONE REMODELING; CALORIC INTAKE; CHRONIC INFLAMMATION; ENERGY EXPENDITURE; ENERGY METABOLISM; FAT MASS; HUMAN; LIPID METABOLISM; MENOPAUSE; MESENCHYMAL STEM CELL; NONHUMAN; OBESITY; OSTEOPOROSIS; PRIORITY JOURNAL; REVIEW; WEIGHT REDUCTION;

Α-LINOLENIC ACID; 2010 DG; 2010 DIETARY GUIDELINES FOR AMERICANS; 5-LIPOXYGENASE; 5-LOX; AA; ACCEPTABLE MACRONUTRIENT DISTRIBUTION RANGES; AHA; ALA; AMDR; AMERICAN HEART ASSOCIATION; ARACHIDONIC ACID; BMD; BONE MINERAL DENSITY; C-REACTIVE PROTEIN; CANNABINOID RECEPTOR TYPE 2; CB2; COX-2; CRP; CYCLOOXYGENASE-2; DHA; DOCOSAHEXAENOIC ACID; DOCOSAPENTAENOIC ACID; DPA; EICOSAPENTAENOIC ACID; EPA; IFNΓ; IL-6; INFLAMMATION; INTERFERON-Γ; INTERLEUKIN-6; LA; LEUKOTRIENE B(4); LEUKOTRIENE B(5); LGCI; LINOLEIC ACID; LOW-GRADE CHRONIC INFLAMMATION; LTB(4); LTB(5); MCP-1; MESENCHYMAL STEM CELL; MESENCHYMAL STEM CELLS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MSC; NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY; NHANES; NITRIC OXIDE; NO; OBESITY; OMEGA-3 FATTY ACIDS; OSTEOPOROSIS; PGE(2); POLYUNSATURATED FATTY ACIDS; PROSTAGLANDIN E2; PUFA; SDA; STEARIDONIC ACID; TNF-Α; TUMOR NECROSIS FACTOR-Α;

ADIPOGENESIS; BONE AND BONES; DIET; DIETARY FATS; DOCOSAHEXAENOIC ACIDS; EICOSAPENTAENOIC ACID; FATTY ACIDS, OMEGA-6; HUMANS; INFLAMMATION; MESENCHYMAL STROMAL CELLS; OBESITY; OSTEOPOROSIS;

EID: 84879887816     PISSN: 02715317     EISSN: 18790739     Source Type: Journal    
DOI: 10.1016/j.nutres.2013.04.012     Document Type: Review

References (153)

1. Simopoulos A.P. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 2006, 60:502-507.
2. Danaei G., Ding E.L., Mozaffarian D., Taylor B., Rehm J., Murray C.J., et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 2009, 6:e1000058.
3. Rosen C.J., Bouxsein M.L. Mechanisms of disease: is osteoporosis the obesity of bone?. Nat Clin Pract Rheumatol 2006, 2:35-43.
4. Maurin A.C., Chavassieux P.M., Vericel E., Meunier P.J. Role of polyunsaturated fatty acids in the inhibitory effect of human adipocytes on osteoblastic proliferation. Bone 2002, 31:260-266.
5. Stenvinkel P., Ketteler M., Johnson R.J., Lindholm B., Pecoits-Filho R., Riella M., et al. IL-10, Il-6, and TNF-alpha: Central factors in the altered cytokine network of uremia-the good, the bad, and the ugly. Kidney Int 2005, 67:1216-1233.
6. Mundy G.R. Pathogenesis of osteoporosis and challenges for drug delivery. Adv Drug Deliv Rev 2000, 42:165-173.
7. Ng A.C., Melton L.J., Atkinson E.J., Achenbach S.J., Holets M.F., Peterson J.M., et al. Relationship of adiposity to bone volumetric density and microstructure in men and women across the adult lifespan. Bone 2013, 55:119-125.
8. Watkins B.A., Li Y., Lippman H.E., Feng S. Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism. Prostaglandins Leukot Essent Fatty Acids 2003, 68:387-398.
9. Watkins B.A., Li Y., Allen K.G., Hoffmann W.E., Seifert M.F. Dietary ratio of (n-6)/(n-3) polyunsaturated fatty acids alters the fatty acid composition of bone compartments and biomarkers of bone formation in rats. J Nutr 2000, 130:2274-2284.
10. Watkins B.A., Li Y., Seifert M.F. Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral and serum biomarkers in ovariectomized rats. J Nutr Biochem 2006, 17:282-289.
11. Kim H.K., Della-Fera M., Lin J., Baile C.A. Docosahexaenoic acid inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 preadipocytes. J Nutr 2006, 136:2965-2969.
12. Flachs P., Horakova O., Brauner P., Rossmeisl M., Pecina P., Franssen-van Hal N., et al. Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia 2005, 48:2365-2375.
13. U.S.Department of Agriculture What we eat in America, NHANES 2007-2008 data: nutrient intakes from food-mean amounts consumed per individual, by gender and age, in the United States, 2007-2008-day 1 dietary intake data, weighted (revised August 2010) [cited 2013 04/13/2013] Available from:. http://www.ars.usda.gov/SP2UserFiles/Place/12355000/pdf/0708/Table_1_NIN_GEN_07.pdf.
14. Inoue K., Kishida K., Hirata A., Funahashi T., Shimomura I. Low serum eicosapentaenoic acid / arachidonic acid ratio in male subjects with visceral obesity. Nutr Metab 2013, 10:25.
15. Mozaffarian D., Lemaitre R.N., King I.B., Song X., Huang H., Sacks F.M., et al. Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. Annals Intern Med 2013, 158:515-525.
16. Liou Y.A., King D.J., Zibrik D., Innis S.M. Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men. J Nutr 2007, 137:945-952.
17. US Dept.of Agriculture, US Dept.of Health and Human Services Report of the dietary guidelines advisory committee on the dietary guidelines for americans, 2010. [last updated 10/21/2011] [cited 2013 04/13/2013] http://www.cnpp.usda.gov/DGAs2010-DGACReport.htm.
18. Institute of Medicine Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (2002-2005). Panel on Macronutrients, Subcommittee on Upper Reference Levels of Nutrients, Subcommittee on Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes 2005, 1573. The National Academies Press, Washington, DC.
19. Kris-Etherton P.M., Harris W.S., Appel L.J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002, 106:2747-2757.
20. Teitelbaum S.L. Postmenopausal osteoporosis, T cells, and immune dysfunction. Proc Natl Acad Sci 2004, 101:16711-16712.
21. De Lorgeril M., Salen P., Martin J.L., Monjaud I., Delaye J., Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon diet heart study. Circulation 1999, 99:779-785.
22. Cordain L., Eaton S.B., Sebastian A., Mann N., Lindeberg S., Watkins B.A., et al. Origins and evolution of the western diet: health implications for the 21st century. Am J Clin Nutr 2005, 81:341-354.
23. Simopoulos A.P. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med 2008, 233:674-688.
24. Serhan C.N., Chiang N., Van Dyke T.E. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 2008, 8:349-361.
25. Appleton K.M., Rogers P.J., Ness A.R. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr 2010, 91:757-770.
26. Kim Y., Ilich J.Z. Implications of dietary alpha-linolenic acid in bone health. Nutrition 2011, 27:1101-1107.
27. Poulsen R.C., Moughan P.J., Kruger M.C. Long-chain polyunsaturated fatty acids and the regulation of bone metabolism. Exp Biol Med 2007, 232:1275-1288.
28. Wei M.Y., Jacobson T.A. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep 2011, 13:474-483.
29. Martinez-Victoria E., Yago M.D. Omega 3 polyunsaturated fatty acids and body weight. Br J Nutr 2012, 107(Suppl 2):S107-S116.
30. Orchard T.S., Pan X., Cheek F., Ing S.W., Jackson R.D. A systematic review of omega-3 fatty acids and osteoporosis. Br J Nutr 2012, 107(Suppl 2):S253-S260.
31. Appleton K.M., Fraser W.D., Rogers P.J., Ness A.R., Tobias J.H. Supplementation with a low-moderate dose of n-3 long-chain pufa has no short-term effect on bone resorption in human adults. Br J Nutr 2011, 105:1145-1149.
32. Hotamisligil G.S. Inflammation and metabolic disorders. Nature 2006, 444:860-867.
33. Woods J.A., Wilund K.R., Martin S.A., Kistler B.M. Exercise, inflammation and aging. Aging Disease 2012, 3:130-140.
34. Ward P. Acute and chronic inflammation. Fundamentals of inflammation 2010, 1-16. Cambridge University Press, New York. C.N. Serhan, P.A. Ward, D.W. Gilroy (Eds.).
35. Gregor M.F., Hotamisligil G.S. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011, 29:415-445.
36. World Health Organization Obesity and overweight fact sheet no. 311. 2011 [cited 2013 4/12/2013] Available from:. http://www.who.int/mediacentre/factsheets/fs311/en/#.
37. Johnell O., Kanis J.A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006, 17:1726-1733.
38. Wolf G. Energy regulation by the skeleton. Nutr Rev 2008, 66:229-233.
39. Karsenty G. Convergence between bone and energy homeostases: leptin regulation of bone mass. Cell Metab 2006, 4:341-348.
40. Yadav V.K., Oury F., Suda N., Liu Z.W., Gao X.B., Confavreux C., et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 2009, 138:976-989.
41. De Vriese C., Hacquebard M., Gregoire F., Carpentier Y., Delporte C. Ghrelin interacts with human plasma lipoproteins. Endocrinology 2007, 148:2355-2362.
42. Briggs D.I., Enriori P.J., Lemus M.B., Cowley M.A., Andrews Z.B. Diet-induced obesity causes ghrelin resistance in arcuate NPY/AGRP neurons. Endocrinology 2010, 151:4745-4755.
43. Reid I.R. Relationships between fat and bone. Osteoporos Int 2008, 19:595-606.
44. Motyl K.J., McCabe L.R., Schwartz A.V. Bone and glucose metabolism: a two-way street. Arch Biochem Biophys 2010, 503:2-10.
45. Neve A., Corrado A., Cantatore F.P. Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol 2013, 228:1149-1153.
46. Mauvais-Jarvis F., Clegg D.J., Hevener A.L. The role of estrogens in control of energy balance and glucose homeostasis. Endocr Rev 2013, [ePub].
47. Foo C., Frey S., Yang H.H., Zellweger R., Filgueira L. Downregulation of beta-catenin and transdifferentiation of human osteoblasts to adipocytes under estrogen deficiency. Gynecol Endocrinol 2007, 23:535-540.
48. Oettel M. Is there a role for estrogens in the maintenance of men's health?. Aging Male 2002, 5:248-257.
49. Bayne S., Jones M.E., Li H., Pinto A.R., Simpson E.R., Liu J.P. Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice. Cell Res 2008, 18:1141-1150.
50. Pignolo R.J., Suda R.K., McMillan E.A., Shen J., Lee S.H., Choi Y., et al. Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis. Aging Cell 2008, 7:23-31.
51. Kiecolt-Glaser J.K., Epel E.S., Belury M.A., Andridge R., Lin J., Glaser R., et al. Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: a randomized controlled trial. Brain Behav Immunity 2013, 28:16-24.
52. Flachs P., Rossmeisl M., Bryhn M., Kopecky J. Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clin Sci 2009, 116:1-16.
53. Chang K., Chang W.H. Pulsed electromagnetic fields prevent osteoporosis in an ovariectomized female rat model: a prostaglandin E2-associated process. Bioelectromagnetics 2003, 24:189-198.
54. Nigam S., Fiore S., Luscinskas F.W., Serhan C.N. Lipoxin A4 and lipoxin B4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: dissociation between lipid remodeling and adhesion. J Cellular Physiol 1990, 143:512-523.
55. Godson C., Mitchell S., Harvey K., Petasis N.A., Hogg N., Brady H.R. Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 2000, 164:1663-1667.
56. Bachi A.L., Kim F.J., Nonogaki S., Carneiro C.R., Lopes J.D., Jasiulionis M.G., et al. Leukotriene B4 creates a favorable microenvironment for murine melanoma growth. Mol Cancer Res 2009, 7:1417-1424.
57. Bagga D., Wang L., Farias-Eisner R., Glaspy J.A., Reddy S.T. Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on Cox-2 expression and IL-6 secretion. Proc Natl Acad Sci 2003, 100:1751-1756.
58. Ariel A., Serhan C.N. Resolvins and protectins in the termination program of acute inflammation. Trends Immunol 2007, 28:176-183.
59. Claria J., Dalli J., Yacoubian S., Gao F., Serhan C.N. Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat. J Immunol 2012, 189:2597-2605.
60. Moreno J.J. Differential effects of arachidonic and eicosapentaenoic acid-derived eicosanoids on polymorphonuclear transmigration across endothelial cell cultures. J Pharmacol Exp Ther 2009, 331:1111-1117.
61. Thusgaard M., Christensen J.H., Morn B., Andersen T.S., Vige R., Arildsen H., et al. Effect of fish oil (n-3 polyunsaturated fatty acids) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy: a randomized, double-blind, placebo-controlled study. Scand J Infect Dis 2009, 41:760-766.
62. Hagi A., Nakayama M., Shinzaki W., Haji S., Ohyanagi H. Effects of the omega-6:omega-3 fatty acid ratio of fat emulsions on the fatty acid composition in cell membranes and the anti-inflammatory action. J Parenter Enteral Nutr 2010, 34:263-270.
63. Tjonahen E., Oh S.F., Siegelman J., Elangovan S., Percarpio K.B., Hong S., et al. Resolvin E2: identification and anti-inflammatory actions: pivotal role of human 5-lipoxygenase in resolvin E series biosynthesis. Chem Biol 2006, 13:1193-1202.
64. Arita M., Bianchini F., Aliberti J., Sher A., Chiang N., Hong S., et al. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 2005, 201:713-722.
65. Herrera B.S., Ohira T., Gao L., Omori K., Yang R., Zhu M., et al. An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption. Br J Pharmacol 2008, 155:1214-1223.
66. Dalli J., Winkler J.W., Colas R.A., Arnardottir H., Cheng C.Y., Chiang N., et al. Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chem Biol 2013, 20:188-201.
67. Levy B.D., Kohli P., Gotlinger K., Haworth O., Hong S., Kazani S., et al. Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J Immunol 2007, 178:496-502.
68. Serhan C.N., Yang R., Martinod K., Kasuga K., Pillai P.S., Porter T.F., et al. Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 2009, 206:15-23.
69. Wymann M.P., Schneiter R. Lipid signalling in disease. Nat Rev Mol Cell Biol 2008, 9:162-176.
70. Stables M.J., Gilroy D.W. Old and new generation lipid mediators in acute inflammation and resolution. Prog Lipid Res 2011, 50:35-51.
71. Folco G., Murphy R.C. Eicosanoid transcellular biosynthesis: from cell-cell interactions to in vivo tissue responses. Pharmacol Rev 2006, 58:375-388.
72. Chen C. Cox-2's new role in inflammation. Nat Chem Biol 2010, 6:401-402.
73. Kellinsalmi M., Parikka V., Risteli J., Hentunen T., Leskela H.V., Lehtonen S., et al. Inhibition of cyclooxygenase-2 down-regulates osteoclast and osteoblast differentiation and favours adipocyte formation in vitro. Eur J Pharmacol 2007, 572:102-110.
74. Werz O., Steinhilber D. Development of 5-lipoxygenase inhibitors-lessons from cellular enzyme regulation. Biochem Pharmacol 2005, 70:327-333.
75. Kobayashi J., Yokoyama S., Kitamura S. Eicosapentaenoic acid modulates arachidonic acid metabolism in rat alveolar macrophages. Prostaglandins Leukot Essent Fatty Acids 1995, 52:259-262.
76. Gallwitz W.E., Mundy G.R., Lee C.H., Qiao M., Roodman G.D., Raftery M., et al. 5-Lipoxygenase metabolites of arachidonic acid stimulate isolated osteoclasts to resorb calcified matrices. J Biol Chem 1993, 268:10087-10094.
77. Schmitz G., Ecker J. The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res 2008, 47:147-155.
78. Lopez-Parra M., Titos E., Horrillo R., Ferre N., Gonzalez-Periz A., Martinez-Clemente M., et al. Regulatory effects of arachidonate 5-lipoxygenase on hepatic microsomal TG transfer protein activity and VLDL-triglyceride and apoB secretion in obese mice. J Lipid Res 2008, 49:2513-2523.
79. Kaaman M., Ryden M., Axelsson T., Nordstrom E., Sicard A., Bouloumie A., et al. ALOX5AP expression, but not gene haplotypes, is associated with obesity and insulin resistance. Int J Obes 2006, 30:447-452.
80. Martinez-Clemente M., Claria J., Titos E. The 5-lipoxygenase/leukotriene pathway in obesity, insulin resistance, and fatty liver disease. Curr Opin Clin Nutr Metabol Care 2011, 14:347-353.
81. Nielsen M.S., Gammelmark A., Madsen T., Obel T., Aardestrup I., Schmidt E.B. The effect of low-dose marine n-3 fatty acids on the biosynthesis of pro-inflammatory 5-lipoxygenase pathway metabolites in overweight subjects: a randomized controlled trial. Prostaglandins Leuko Essent Fatty Acids 2012, 87:43-48.
82. Martel-Pelletier J., Mineau F., Fahmi H., Laufer S., Reboul P., Boileau C., et al. Regulation of the expression of 5-lipoxygenase-activating protein/5-lipoxygenase and the synthesis of leukotriene B(4) in osteoarthritic chondrocytes: role of transforming growth factor beta and eicosanoids. Arthritis Rheum 2004, 50:3925-3933.
83. Rossi A., Pergola C., Koeberle A., Hoffmann M., Dehm F., Bramanti P., et al. The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages. Br J Pharmacol 2010, 161:555-570.
84. Fan C., Liu X., Shen W., Deckelbaum R.J., Qi K. The regulation of leptin, leptin receptor and pro-opiomelanocortin expression by n-3 PUFAs in diet-induced obese mice is not related to the methylation of their promoters. Nutr Metab 2011, 8:31.
85. Di Benedetto R., Salvati S., Attorri L., Di Biase A. Omega-3 polyunsaturated fatty acids affect leptin receptor gene expression in pituitary GH4C1 cell line. J Food Lipids 2009, 16:382-393.
86. Schwinkendorf D.R., Tsatsos N.G., Gosnell B.A., Mashek D.G. Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism. Int J Obes 2011, 35:336-344.
87. Silvestri C., Di Marzo V. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Cell Metab 2013, 17:475-490.
88. Di Marzo V. Endocannabinoids: synthesis and degradation. Rev Physiol Biochem Pharmacol 2008, 160:1-24.
89. Lafourcade M., Larrieu T., Mato S., Duffaud A., Sepers M., Matias I., et al. Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nat Neurosci 2011, 14:345-350.
90. Matias I., Bisogno T., Di Marzo V. Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake. Int J Obes 2006, 30:S7-S12.
91. Batetta B., Griinari M., Carta G., Murru E., Ligresti A., Cordeddu L., et al. Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats. J Nutr 2009, 139:1495-1501.
92. Cinti S. Histopathology of the obese adipose organ. J Anat Embryol 2011, 116:44.
93. Cancello R., Clement K. Is obesity an inflammatory illness? Role of low-grade inflammation and macrophage infiltration in human white adipose tissue. BJOG 2006, 113:1141-1147.
94. Itariu B.K., Zeyda M., Leitner L., Marculescu R., Stulnig T.M. Treatment with n-3 polyunsaturated fatty acids overcomes the inverse association of vitamin D deficiency with inflammation in severely obese patients: a randomized controlled trial. PLoS One 2013, 8:e54634.
95. Tsitouras P.D., Gucciardo F., Salbe A.D., Heward C., Harman S.M. High omega-3 fat intake improves insulin sensitivity and reduces CRP and IL-6, but does not affect other endocrine axes in healthy older adults. Horm Metab Res 2008, 40:199-205.
96. Itariu B.K., Zeyda M., Hochbrugger E.E., Neuhofer A., Prager G., Schindler K., et al. Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial. Am J Clin Nutr 2012, 96:1137-1149.
97. Spencer M., Finlin B.S., Unal R., Zhu B., Morris A.J., Shipp L.R., et al. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes 2013, 62:1709-1717.
98. Monk J.M., Hou T.Y., Turk H.F., Weeks B., Wu C., McMurray D.N., et al. Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated TH17 cell-mediated inflammation during colitis. PLoS One 2012, 7:e49739.
99. Kalupahana N.S., Claycombe K., Newman S.J., Stewart T., Siriwardhana N., Matthan N., et al. Eicosapentaenoic acid prevents and reverses insulin resistance in high-fat diet-induced obese mice via modulation of adipose tissue inflammation. J Nutr 2010, 140:1915-1922.
100. Hsueh H.W., Zhou Z., Whelan J., Allen K.G., Moustaid-Moussa N., Kim H., et al. Claycombe KJ. Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via toll-like receptor-2-mediated pathways. J Nutr 2011, 141:1260-1266.
101. Petersson H., Basu S., Cederholm T., Riserus U. Serum fatty acid composition and indices of stearoyl-Co-A desaturase activity are associated with systemic inflammation: longitudinal analyses in middle-aged men. Br J Nutr 2008, 99:1186-1189.
102. Petersson H., Lind L., Hulthe J., Elmgren A., Cederholm T., Riserus U. Relationships between serum fatty acid composition and multiple markers of inflammation and endothelial function in an elderly population. Atherosclerosis 2009, 203:298-303.
103. Ailhaud G., Guesnet P. Fatty acid composition of fats is an early determinant of childhood obesity: a short review and an opinion. Obes Rev 2004, 5:21-26.
104. Madsen L., Pedersen L.M., Liaset B., Ma T., Petersen R.K., Van Den Berg S., et al. cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids. J Biol Chem 2008, 283:7196-7205.
105. Thorsdottir I., Tomasson H., Gunnarsdottir I., Gisladottir E., Kiely M., Parra M.D., et al. Randomized trial of weight-loss-diets for young adults varying in fish and fish oil content. Int J Obes 2007, 31:1560-1566.
106. Munro I.A., Garg M.L. Prior supplementation with long chain omega-3 polyunsaturated fatty acids promotes weight loss in obese adults: a double-blinded randomised controlled trial. Food Funct 2013, 4:650-658.
107. Gao Y., Qian W.-P., Dark K., Toraldo G., Lin A.S.P., Guldberg R.E., et al. Estrogen prevents bone loss through transforming growth factor β signaling in T cells. Proc Natl Acad Sci USA 2004, 101:16618-16623.
108. Ferrari-Lacraz S., Burger D. Ranking bone resorption versus inflammation: infection makes the decision. IBMS BoneKEy 2010, 7:156-160.
109. Jeon Y.K., Lee J.G., Kim S.S., Kim B.H., Kim S.J., Kim Y.K., et al. Association between bone mineral density and metabolic syndrome in pre- and postmenopausal women. Endocr J 2011, 58:87-93.
110. Ding C., Parameswaran V., Udayan R., Burgess J., Jones G. Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab 2008, 93:1952-1958.
111. Shen C.L., Peterson J., Tatum O.L., Dunn D.M. Effect of long-chain n-3 polyunsaturated fatty acid on inflammation mediators during osteoblastogenesis. J Med Food 2008, 11:105-110.
112. Yuan J., Akiyama M., Nakahama K., Sato T., Uematsu H., Morita I. The effects of polyunsaturated fatty acids and their metabolites on osteoclastogenesis in vitro. Prostaglandins Other Lipid Mediat 2010, 92:85-90.
113. Kruger M.C., Coetzee M., Haag M., Weiler H. Long-chain polyunsaturated fatty acids: selected mechanisms of action on bone. Prog Lipid Res 2010, 49:438-449.
114. Priante G., Bordin L., Musacchio E., Clari G., Baggio B. Fatty acids and cytokine mRNA expression in human osteoblastic cells: a specific effect of arachidonic acid. Clin Sci 2002, 102:403-409.
115. Musacchio E., Priante G., Budakovic A., Baggio B. Effects of unsaturated free fatty acids on adhesion and on gene expression of extracellular matrix macromolecules in human osteoblast-like cell cultures. Connect Tissue Res 2007, 48:34-38.
116. Li Y., Seifert M.F., Lim S.Y., Salem N., Watkins B.A. Bone mineral content is positively correlated to n-3 fatty acids in the femur of growing rats. Br J Nutr 2010, 104:674-685.
117. Jarvinen R., Tuppurainen M., Erkkila A.T., Penttinen P., Karkkainen M., Salovaara K., et al. Associations of dietary polyunsaturated fatty acids with bone mineral density in elderly women. Eur J Clin Nutr 2012, 66:496-503.
118. Hutchins H.L., Li Y., Hannon K., Watkins B.A. Eicosapentaenoic acid decreases expression of anandamide synthesis enzyme and cannabinoid receptor 2 in osteoblast-like cells. J Nutr Biochem 2011, 22:195-200.
119. Ofek O., Karsak M., Leclerc N., Fogel M., Frenkel B., Wright K., et al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci 2006, 103:696-701.
120. Raggatt L.J., Partridge N.C. Cellular and molecular mechanisms of bone remodeling. J Biol Chem 2010, 285:25103-25108.
121. Izadpanah R., Trygg C., Patel B., Kriedt C., Dufour J., Gimble J.M., et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 2006, 99:1285-1297.
122. Das U.N. Essential fatty acids and their metabolites as modulators of stem cell biology with reference to inflammation, cancer, and metastasis. Cancer Metastasis Rev 2011, 30:311-324.
123. Lepperdinger G. Inflammation and mesenchymal stem cell aging. Curr Opin Immunol 2011, 23:518-524.
124. Laschober G.T., Brunauer R., Jamnig A., Singh S., Hafen U., Fehrer C., et al. Age-specific changes of mesenchymal stem cells are paralleled by upregulation of CD106 expression as a response to an inflammatory environment. Rejuvenation Res 2011, 14:119-131.
125. Ackert-Bicknell C., Rosen C. The genetics of PPARγ and the skeleton. PPAR Res 2006, 93258.
126. Aleshin S., Grabeklis S., Hanck T., Sergeeva M., Reiser G. Peroxisome proliferator-activated receptor (PPAR)-gamma positively controls and PPARalpha negatively controls cyclooxygenase-2 expression in rat brain astrocytes through a convergence on PPARbeta/delta via mutual control of PPAR expression levels. Mol Pharmacol 2009, 76:414-424.
127. Lecka-Czernik B., Suva L.J. Resolving the two "bony" faces of PPAR-gamma. PPAR Res 2006, 2006:27489.
128. Metzger D., Imai T., Jiang M., Takukawa R., Desvergne B., Wahli W., et al. Functional role of RXRs and PPARgamma in mature adipocytes. Prostaglandins Leukot Essent Fatty Acids 2005, 73:51-58.
129. Takazawa T., Yamauchi T., Tsuchida A., Takata M., Hada Y., Iwabu M., et al. Peroxisome proliferator-activated receptor gamma agonist rosiglitazone increases expression of very low density lipoprotein receptor gene in adipocytes. J Biol Chem 2009, 284:30049-30057.
130. Yu S., Reddy J.K. Transcription coactivators for peroxisome proliferator-activated receptors. Biochim Biophys Acta 2007, 1771:936-951.
131. Cawthorn W.P., Sethi J.K. TNF-alpha and adipocyte biology. FEBS Lett 2008, 582:117-131.
132. Mukai T., Otsuka F., Otani H., Yamashita M., Takasugi K., Inagaki K., et al. TNF-alpha inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling. Biochem Biophys Res Commun 2007, 356:1004-1010.
133. Robinson L.J., Borysenko C.W., Blair H.C. Tumor necrosis factor family receptors regulating bone turnover: new observations in osteoblastic and osteoclastic cell lines. Ann N Y Acad Sci 2007, 1116:432-443.
134. Zahorska-Markiewicz B., Janowska J., Olszanecka-Glinianowicz M., Zurakowski A. Serum concentrations of TNF-alpha and soluble TNF-alpha receptors in obesity. Int J Obes Relat Metab Disord 2000, 24:1392-1395.
135. Guebre-Egziabher F., Rabasa-Lhoret R., Bonnet F., Bastard J.P., Desage M., Skilton M.R., et al. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. Eur J Clin Nutr 2008, 62:1287-1293.
136. Isenmann S., Cakouros D., Zannettino A., Shi S., Gronthos S. hTERT transcription is repressed by Cbfa1 in human mesenchymal stem cell populations. J Bone Miner Res 2007, 22:897-906.
137. Jeong J.H., Jung Y.K., Kim H.J., Jin J.S., Kim H.N., Kang S.M., et al. The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of Runx2 in skeletal tissues. Mol Cell Biol 2010, 30:2365-2375.
138. Zaidi S.K., Pande S., Pratap J., Gaur T., Grigoriu S., Ali S.A., et al. Runx2 deficiency and defective subnuclear targeting bypass senescence to promote immortalization and tumorigenic potential. Proc Natl Acad Sci 2007, 104:19861-19866.
139. McCarthy T.L., Chang W.Z., Liu Y., Centrella M. Runx2 integrates estrogen activity in osteoblasts. J Biol Chem 2003, 278:43121-43129.
140. Zhang X., Schwarz E.M., Young D.A., Puzas J.E., Rosier R.N., O'Keefe R.J. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest 2002, 109:1405-1415.
141. Ramirez-Yanez G.O., Hamlet S., Jonarta A., Seymour G.J., Symons A.L. Prostaglandin E2 enhances transforming growth factor-beta 1 and TGF-beta receptors synthesis: an in vivo and in vitro study. Prostaglandins Leukot Essent Fatty Acids 2006, 74:183-192.
142. Cao Y. Angiogenesis modulates adipogenesis and obesity. J Clin Invest 2007, 117:2362-2368.
143. Clarke D.C., Liu X. Decoding the quantitative nature of TGF-beta/Smad signaling. Trends Cell Biol 2008, 18:430-442.
144. Fain J.N. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm 2006, 74:443-477.
145. Ng F., Boucher S., Koh S., Sastry K.S., Chase L., Lakshmipathy U., et al. PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. Blood 2008, 112:295-307.
146. Zhao L.-J., Jiang H., Papasian C.J., Maulik D., Drees B., Hamilton J., et al. Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res 2008, 23:17.
147. DiBattista J.A., Dore S., Morin N., Abribat T. Prostaglandin E2 up-regulates insulin-like growth factor binding protein-3 expression and synthesis in human articular chondrocytes by a c-AMP-independent pathway: role of calcium and protein kinase A and C. J Cell Biochem 1996, 63:320-333.
148. Kelly O., Cusack S., Jewell C., Cashman K.D. The effect of polyunsaturated fatty acids, including conjugated linoleic acid, on calcium absorption and bone metabolism and composition in young growing rats. Br J Nutr 2003, 90:743-750.
149. Kaaks R. Nutrition, insulin, IGF-1 metabolism and cancer risk: a summary of epidemiological evidence. Novartis Found Symp 2004, 262(247-60):60-68.
150. Landin-Wilhelmsen K., Wilhelmsen L., Bengtsson B.A. Postmenopausal osteoporosis is more related to hormonal aberrations than to lifestyle factors. Clin Endocrinol 1999, 51:387-394.
151. Sandhu M.S., Gibson J.M., Heald A.H., Dunger D.B., Wareham N.J. Association between insulin-like growth factor-I: insulin-like growth factor-binding protein-1 ratio and metabolic and anthropometric factors in men and women. Cancer Epidemiol Biomarkers Prev 2004, 13:166-170.
152. Serhan C.N., Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005, 6:1191-1197.
153. McDaniel J.C., Belury M., Ahijevych K., Blakely W. Omega-3 fatty acids effect on wound healing. Wound Repair Regen 2008, 16:337-345.