Epigenetics and nutrition-related epidemics of metabolic diseases: Current perspectives and challenges

Food and Chemical Toxicology

Volumn 96, Issue , 2016, Pages 191-204

  Hernández Aguilera, Anna ^a   Fernández Arroyo, Salvador ^a   Cuyàs, Elisabet ^b,c   Luciano Mateo, Fedra ^a   Cabre, Noemi ^a   Camps, Jordi ^a   Lopez Miranda, Jose ^d,e   Menendez, Javier A ^b,c   Joven, Jorge ^a,f  

^a HOSPITAL UNIVERSITARI SANT JOAN DE REUS   (Spain)

^b GIRONA BIOMEDICAL RESEARCH INSTITUTE IDIBGI   (Spain)

^c CATALAN INSTITUTE OF ONCOLOGY   (Spain)

^d HOSPITAL UNIVERSITARIO REINA SOFÍA   (Spain)

^e Instituto de Salud Carlos III   (Spain)

^f The Campus of International Excellence Southern Catalonia ^*  (Spain)

Author keywords

Diabetes; DNA methylation; Epigenetics; Metabolomics; Nutrient toxicity; Obesity

Indexed keywords

CARBON METABOLISM; CHROMATIN STRUCTURE; DIABETES MELLITUS; DNA METHYLATION; ENERGY METABOLISM; EPIGENETICS; FOOD INTAKE; HEALTH; HUMAN; INFLAMMATION; INHERITANCE; INSULIN RESISTANCE; METABOLIC DISORDER; METABOLITE; METABOLOMICS; MITOCHONDRION; NONHUMAN; NUTRITION; OBESITY; REVIEW; DISEASE PREDISPOSITION; GENETIC EPIGENESIS; GENETICS; METABOLIC DISEASES; PHYSIOLOGY;

DISEASE SUSCEPTIBILITY; EPIGENESIS, GENETIC; HUMANS; METABOLIC DISEASES; NUTRITIONAL PHYSIOLOGICAL PHENOMENA;

EID: 84981508142     PISSN: 02786915     EISSN: 18736351     Source Type: Journal    
DOI: 10.1016/j.fct.2016.08.006     Document Type: Review

References (180)

1. Ahrens, M., Ammerpohl, O., von Schönfels, W., Kolarova, J., Bens, S., Itzel, T., et al. DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery. Cell Metab. 18 (2013), 296–302.
2. Albert, V., Hall, M.N., mTOR signaling in cellular and organismal energetics. Curr. Opin. Cell Biol. 33 (2015), 55–66.
3. Alexandrou, A., Armeni, E., Kaparos, G., Rizos, D., Tsoka, E., Deligeoroglou, E., et al. Bsm1 vitamin D receptor polymorphism and calcium homeostasis following bariatric surgery. J. Investig. Surg. 28 (2015), 8–17.
4. Alonso-Villaverde, C., Menéndez, J.A., Joven, J., Metabolic stress in infected cells may represent a therapeutic target for human immunodeficiency virus infection. Med. Hypotheses 8 (2013), 125–130.
5. Ambatipudi, S., Cuenin, C., Hernandez-Vargas, H., Ghantous, A., Le Calvez-Kelm, F., Kaask, R., et al. Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study. Epigenomics 8 (2016), 599–618.
6. Anthony, T.G., Morrison, C.D., Gettys, T.W., Remodeling of lipid metabolism by dietary restriction of essential amino acids. Diabetes 62 (2013), 2635–2644.
7. Arora, T., Velagapudi, V., Pournaras, D.J., Welbourn, R., le Roux, C.W., Orešič, M., et al. Roux-en-Y gastric bypass surgery induces early plasma metabolomic and lipidomic alterations in humans associated with diabetes remission. PLoS One, 10, 2015, 10.1371/journal.pone.0126401.
8. Bandstein, M., Mwinyi, J., Ernst, B., Thurnheer, M., Schultes, B., Schiöth, H.B., A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery. Scand. J. Gastroenterol. 51 (2016), 1050–1055.
9. Barger, J.L., Anderson, R.M., Newton, M.A., da Silva, C., Vann, J.A., Pugh, T.D., et al. A conserved transcriptional signature of delayed aging and reduced disease vulnerability is partially mediated by SIRT3. PLoS One, 10, 2015, e0120738.
10. Barlow, A.D., Thomas, D.C., Autophagy in diabetes: β-cell dysfunction, insulin resistance, and complications. DNA Cell Biol. 34 (2015), 252–260.
11. Barres, R., Kirchner, H., Rasmussen, M., Yan, J., Kantor, F.R., Krook, A., et al. Weight loss after gastric bypass surgery in human obesity remodels promoter methylation. Cell Rep. 3 (2013), 1020–1027.
12. Barth, T.K., Imhof, A., Fast signals and slow marks: the dynamics of histone modifications. Trends Biochem. Sci. 35 (2010), 618–626.
13. Bell, O., Tiwari, V.K., Thomä, N.H., Schübeler, D., Determinants and dynamics of genome accessibility. Nat. Rev. Genet. 12 (2011), 554–564.
14. Beltrán-Debón, R., Rodríguez-Gallego, E., Fernández-Arroyo, S., Senan- Campos, O., Massucci, F.A., Hernández-Aguilera, A., et al. The acute impact of polyphenols from Hibiscus sabdariffa in metabolic homeostasis: an approach combining metabolomics and gene- expression analyses. Food Funct. 6 (2015), 2957–2966.
15. Benayoun, B.A., Pollina, E., Brunet, A., Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat. Rev. Mol. Cell Biol. 16 (2015), 593–610.
16. Benton, M.C., Johnstone, A., Eccles, D., Harmon, B., Hayes, M.T., Lea, R.A., et al. An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss. Genome Biol., 22(16), 2015, 8.
17. Bernstein, L.E., Berry, J., Kim, S., Canavan, B., Grinspoon, S.K., Effects of etanercept in patients with the metabolic syndrome. Arch. Intern. Med. 166 (2006), 902–908.
18. Blewitt, M.E., Vickaryous, N.K., Paldi, A., Koseki, H., Whitelaw, E., Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet., 2, 2006, e49.
19. Blumberg, R., Powrie, F., Microbiota, disease, and back to health: a metastable journey. Sci. Transl. Med., 4, 2012 137rv137.
20. Bravata, D.M., Sanders, L., Huang, J., Krumholz, H.M., Olkin, I., Gardner, C.D., et al. Efficacy and safety of low-carbohydrate diets: a systematic review. J. Am. Med. Assoc. 289 (2003), 1837–1850.
21. Burcelin, R., Garidou, L., Pomie, C., Immuno-microbiota cross and talk: the new paradigm of metabolic diseases. Semin. Immunol. 24 (2012), 67–74.
22. Cai, T.Q., Ren, N., Jin, L., Cheng, K., Kash, S., Chen, R., et al. Role of GPR81 in lactate-mediated reduction of adipose lipolysis. Biochem. Biophys. Res. Commun. 377 (2008), 987–991.
23. Calvo, N., Beltrán-Debón, R., Rodríguez-Gallego, E., Hernández-Aguilera, A., Guirro, M., Mariné-Casadó, R., et al. Liver fat deposition and mitochondrial dysfunction in morbid obesity: an approach combining metabolomics with liver imaging and histology. World J. Gastroenterol. 21 (2015), 7529–7544.
24. Camps, J., García-Heredia, A., Hernández-Aguilera, A., Joven, J., Paraoxonases, mitochondrial dysfunction and non-communicable diseases. Chem. Biol. Interact., 2016, 10.1016/j.cbi.2016.04.005.
25. Cefalu, W.T., Rubino, F., Cummings, D.E., Metabolic surgery for type 2 diabetes: changing the landscape of diabetes care. Diabetes Care 39 (2016), 857–860.
26. Chen, H., Orozco, L.D., Wang, J., Rau, C.D., Rubbi, L., Ren, S., et al. DNA methylation indicates susceptibility to isoproterenol-induced cardiac pathology and is associated with chromatin states. Circ. Res. 118 (2016), 786–797.
27. Cheng, Z., Almeida, F.A., Mitochondrial alteration in type 2 diabetes and obesity: an epigenetic link. Cell Cycle 13 (2014), 890–897.
28. Chin, R.M., Fu, X., Pai, M.Y., Vergnes, L., Hwang, H., Deng, G., et al. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP-syntha se and TOR. Nature 510 (2014), 397–401.
29. Cooney, C.A., Dave, A.A., Wolff, G.L., Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring. J. Nutr. 132:8 Suppl. l (2002), 2393S–2400S.
30. Cordero, P., Li, J., Oben, J.A., Epigenetics of obesity: beyond the genome sequence. Curr. Opin. Clin. Nutr. Metab. Care 18 (2015), 361–366.
31. Corominas-Faja, B., Quirantes-Pine, R., Oliveras-Ferraros, C., Vazquez-Martin, A., Cufi, S., Martin-Castillo, B., et al. Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs. Aging 4 (2012), 480–498.
32. Cropley, J.E., Suter, C.M., Beckman, K.B., Martin, D.I., Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation. Proc. Natl. Acad. Sci. U. S. A. 103 (2006), 17308–17312.
33. Cuyàs, E., Fernández-Arroyo, S., Corominas-Faja, B., Rodríguez-Gallego, E., Bosch-Barrera, J., Martin-Castillo, B., et al. Oncometabolic mutation IDH1 R132H confers a metformin-hypersensitive phenotype. Oncotarget 6 (2015), 12279–12296.
34. Dahlman, I., Sinha, I., Gao, H., Brodin, D., Thorell, A., Rydén, M., et al. The fat cell epigenetic signature in post-obese women is characterized by global hypomethylation and differential DNA methylation of adipogenesis genes. Int. J. Obes. (Lond) 39 (2015), 910–919.
35. Darby, W.J., Early concepts on the role of nutrition, diet and longevity. Prog. Clin. Biol. Res. 326 (1990), 1–20.
36. Davidson, L.E., Adams, T.D., Kim, J., Jones, J.L., Hashibe, M., Taylor, D., et al. Association of patient age at gastric bypass surgery with long-term all-cause and cause-specific mortality. JAMA Surg., 2016, 10.1001/jamasurg.2015.5501 2016 Feb 10.
37. Dawson, M.A., Kouzarides, T., Cancer epigenetics: from mechanism to therapy. Cell 150 (2012), 12–27.
38. de Luis, D.A., Aller, R., Sagrado, M.G., Izaola, O., Terroba, M.C., Cuellar, L., et al. Influence of lys656asn polymorphism of leptin receptor gene on surgical results of biliopancreatic diversion. J. Gastrointest. Surg. 14 (2010), 899–903.
39. de Luis, D.A., Sagrado, M.G., Pacheco, D., Terroba, M.C., Martin, T., Cuellar, L., et al. Effects of C358A missense polymorphism of the endocannabinoid segrading enzyme fatty acid amide hydrolase on weight loss and cardiovascular risk factors 1 year after biliopancreatic diversion surgery. Surg. Obes. Relat. Dis. 6 (2010), 516–520.
40. de Mello, V.D., Pulkkinen, L., Lalli, M., Kolehmainen, M., Pihlajamäki, J., Uusitupa, M., DNA methylation in obesity and type 2 diabetes. Ann. Med. 46 (2014), 103–113.
41. Deeks, S.G., HIV infection, inflammation, immunosenescence, and aging. Annu. Rev. Med. 62 (2011), 141–155.
42. Del Barco, S., Vazquez-Martin, A., Cufí, S., Oliveras-Ferraros, C., Bosch-Barrera, J., Joven, J., et al. Metformin: multi-faceted protection against cancer. Oncotarget 2 (2011), 896–917.
43. Donkin, I., Versteyhe, S., Ingerslev, L.R., Qian, K., Mechta, M., Nordkap, L., et al. Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metab. 23 (2016), 369–378.
44. Ducker, G.S., Chen, L., Morscher, R.J., Ghergurovich, J.M., Esposito, M., Teng, X., et al. Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway. Cell Metab. 23 (2016), 1–14.
45. Dumas, M.E., Metabolome 2.0: quantitative genetics and network biology of metabolic phenotypes. Mol. Biosyst. 8 (2012), 2494–2502.
46. Ferguson, M., Sohal, B.H., Forster, M.J., Sohal, R.S., Effect of long-term caloric restriction on oxygen consumption and body temperature in two different strains of mice. Mec. Ageing Dev. 128 (2007), 539–545.
47. Fernández-Arroyo, S., Cuyàs, E., Bosch-Barrera, J., Alarcón, T., Joven, J., Menendez, J.A., Activation of the methylation cycle in cells reprogrammed into a stem cell-like state. Oncoscience 2 (2016), 958–967.
48. Finkel, T., The metabolic regulation of aging. Nat. Med. 21 (2015), 1416–1423.
49. Finkel, T., Menazza, S., Holmström, K.M., Parks, R.J., Liu, J., Sun, J., et al. The ins and outs of mitochondrial calcium. Circ. Res. 116 (2015), 1810–1819.
50. Fitzgibbons, T.P., Czech, M.P., Emerging evidence for beneficial macrophage functions in atherosclerosis and obesity-induced insulin resistance. J. Mol. Med. 94 (2016), 267–275.
51. Fontana, L., Partridge, L., Promoting health and longevity through diet: from model organisms to humans. Cell 161 (2015), 106–118.
52. Foster, G.D., Wyatt, H.R., Hill, J.O., Makris, A.P., Rosenbaum, D.L., Brill, C., et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann. Intern. Med. 153 (2010), 147–157.
53. Foulks, J.M., Parnell, K.M., Nix, R.N., Chau, S., Swierczek, K., Saunders, M., et al. Epigenetic drug discovery: targeting DNA methyltransferases. J. Biomol. Screen 17 (2012), 2–17.
54. Gardner, C.D., Kiazand, A., Alhassan, S., Kim, S., Stafford, R.S., Balise, R.R., et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z weight loss study: a randomized trial. J. Am. Med. Assoc. 297 (2007), 969–977.
55. Glossop, J.R., Emes, R.D., Nixon, N.B., Packham, J.C., Fryer, A.A., Mattey, D.L., et al. Genome-wide profiling in treatment-naïve early rheumatoid arthritis reveals DNA methylome changes in T and B lymphocytes. Epigenomics 8 (2016), 209–224.
56. Goldfine, A.B., Fonseca, V., Jablonski, K.A., Pyle, L., Staten, M.A., Shoelson, S.E., TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team, The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann. Intern. Med. 152 (2010), 346–357.
57. Gonzalez, N.S., Communi, D., Hannedouche, S., Boeynaems, J.M., The fate of P2Y-related orphan receptors: GPR80/99 and GPR91 are receptors of dicarboxylic acids. Purinergic Signal. 1 (2004), 17–20.
58. Goodwin, P.J., Ligibel, J.A., Stambolic, V., Metformin in breast cancer: time for action. J. Clin. Oncol. 27 (2009), 3271–3273.
59. Gorder, D.D., Dolecek, T.A., Coleman, G.G., Tillotson, J.L., Brown, H.B., Lenz- Litzow, K., et al. Dietary intake in the Multiple Risk Factor Intervention Trial (MRFIT): nutrient and food group changes over 6 years. J. Am. Diet. Assoc. 86 (1986), 744–751.
60. Gralka, E., Luchinat, C., Tenori, L., Ernst, B., Thurnheer, M., Schultes, B., Metabolomic fingerprint of severe obesity is dynamically affected by bariatric surgery in a procedure-dependent manner. Am. J. Clin. Nutr. 102 (2015), 1313–1322.
61. Grandjean, V., Fourre, S., De Abreu, D.A., Derieppe, M.A., Remy, J.J., Rassoulzadegan, M., RNA-mediated paternal heredity of diet induced obesity and metabolic disorders. Sci. Rep., 5, 2015, 18193.
62. Gross, A.M., Jaeger, P.A., Kreisberg, J.F., Licon, K., Jepsen, K.L., Khosroheidari, M., et al. Methylome-wide analysis of chronic HIV infection reveals five-year increase in biological age and epigenetic targeting of HLA. Mol. Cell. 62 (2016), 157–168.
63. Guénard, F., Deshaies, Y., Cianflone, K., Kral, J.G., Marceau, P., Vohl, M.C., Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 11439–11444.
64. Guo, B., Zhai, D., Cabezas, E., Welsh, K., Nouraini, S., Satterthwait, A.C., et al. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature 423 (2003), 456–461.
65. Gut, P., Verdin, E., The nexus of chromatin regulation and intermediary metabolism. Nature 502 (2013), 489–498.
66. Haas, R., Smith, J., Rocher-Ros, V., Nadkarni, S., Montero-Melendez, T., D'Acquisto, F., et al. Lactate regulates metabolic and pro- inflammatory circuits in Control of T Cell migration and effector functions. PLoS Biol., 13(7), 2015, e1002202 2015 Jul 16.
67. Haas, R., Cucchi, D., Smith, J., Pucino, V., Macdougall, C.E., Mauro, C., Intermediates of metabolism: from bystanders to signalling molecules. Trends biochem. Sci. 41 (2016), 460–471.
68. Hamilton, M.T., Hamilton, D.G., Zderic, T.W., Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes 56 (2007), 2655–2667.
69. Hannum, G., Guinney, J., Zhao, L., Zhang, L., Hughes, G., Sadda, S., et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell. 49 (2013), 359–367.
70. Hardie, D.G., Schaffer, B.E., Brunet, A., AMPK: an energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol. 26 (2016), 190–201.
71. Hashimoto, T., Hussien, R., Brooks, G.A., Colocalization of MCT1, CD147, and LDH in mitochondrial inner membrane of L6 muscle cells: evidence of a mitochondrial lactate oxidation complex. Am. J. Physiol. Endocrinol. Metab. 290 (2006), E1237–E1244.
72. Hatoum, I.J., Greenawalt, D.M., Cotsapas, C., Daly, M.J., Reitman, M.L., Kaplan, L.M., Weight loss after gastric bypass is associated with a variant at 15q26.1. Am. J. Hum. Genet. 92 (2013), 827–834.
73. He, W., Miao, F.J., Lin, D.C., Schwandner, R.T., Wang, Z., Gao, J., et al. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature 429 (2004), 188–193.
74. Heijmans, B.T., Tobi, E.W., Stein, A.D., Putter, H., Blauw, G.J., Susser, E.S., et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 17046–17049.
75. Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W.Z., Strowig, T., et al. Inflammasome mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482 (2012), 179–185.
76. Hernández-Aguilera, A., Rull, A., Rodríguez-Gallego, E., Riera-Borrull, M., Luciano-Mateo, F., Camps, J., et al. Mitochondrial dysfunction: a basic mechanism in inflammation-related non-communicable diseases and therapeutic opportunities. Mediat. Inflamm., 2013(2013), 2013, 135698.
77. Horng, T., Hotamisligil, G.S., Linking the inflammasome to obesity-related disease. Nat. Med. 17 (2011), 164–165.
78. Horvath, S., Erhart, W., Brosch, M., Ammerpohl, O., von Schönfels, W., Ahrens, M., et al. Obesity accelerates epigenetic aging of human liver. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 15538–15543.
79. Horvath, S., Garagnani, P., Bacalini, M.G., Pirazzini, C., Salvioli, S., Gentilini, D., et al. Accelerated epigenetic aging in down syndrome. Aging Cell. 14 (2015), 491–495.
80. Houtkooper, R.H., Argmann, C., Houten, S.M., Canto, C., Jeninga, E.H., Andreux, P.A., et al. The metabolic footprint of aging in mice. Sci. Rep., 1, 2011, 134.
81. Howell, T.H., The art of living long by Luigi Cornaro. Age Ageing 16 (1987), 194–195.
82. Hubbard, B.P., Sinclair, D.A., Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol. Sci. 35 (2014), 146–154.
83. Huypens, P., Sass, S., Wu, M., Dyckhoff, D., Tschöp, M., Theis, F., et al. Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nat. Genet. 48 (2016), 497–499.
84. + and sirtuins in age and disease. Trends Cell Biol. 24 (2014), 464–471.
85. Jacobsen, S.C., Brøns, C., Bork-Jensen, J., Ribel-Madsen, R., Yang, B., Lara, E., et al. Effects of short-term high-fat overfeeding on genome- wide DNA methylation in the skeletal muscle of healthy young men. Diabetologia 55 (2012), 3341–3349.
86. Jha, A.K., Huang, S.C., Sergushichev, A., Lampropoulou, V., Ivanova, Y., Loginicheva, E., et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42 (2015), 419–430.
87. Johnson, A.M.F., Olefsky, J.M., The origins and drivers of insulin resistance. Cell 152 (2013), 673–684.
88. Joven, J., Rull, A., Ferré, N., Escolà-Gil, J.C., Marsillach, J., Coll, B., et al. The results in rodent models of atherosclerosis are not interchangeable: the influence of diet and strain. Atherosclerosis 195 (2007), e85–92.
89. Kaati, G., Bygren, L.O., Edvinsson, S., Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period. Eur. J. Hum. Genet. 10 (2002), 682–688.
90. Kasznicki, J., Sliwinska, A., Drzewoski, J., Metformin in cancer prevention and therapy. Ann. Transl. Med., 6, 2014, 57.
91. Katada, S., Imhof, A., Sassone-Corsi, P., Connecting threads: epigenetics and metabolism. Cell 148 (2012), 24–28.
92. Katoh, Y., Ikura, T., Hoshikawa, Y., Tashiro, S., Ito, T., Ohta, M., et al. Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein. Mol. Cell. 41 (2011), 554–566.
93. Kau, A.L., Ahern, P.P., Griffin, N.W., Goodman, A.L., Gordon, J.I., Human nutrition, the gut microbiome and the immune system. Nature 474 (2011), 327–336.
94. Kirchner, H., Osler, M.E., Krook, A., Zierath, J.R., Epigenetic flexibility in metabolic regulation: disease cause and prevention?. Trends Cell Biol. 23 (2013), 203–209.
95. Klosin, A., Lehner, B., Mechanisms, timescales and principles of trans- generational epigenetic inheritance in animals. Curr. Opin. Genet. Dev. 36 (2016), 41–49.
96. Kristanc, L., Kreft, S., European medicinal and edible plants associated with subacute and chronic toxicity part I: plants with carcinogenic, teratogenic and endocrine-disrupting effects. Food Chem. Toxicol. 92 (2016), 150–164.
97. Lee, S., Muniyappa, R., Yan, X., Chen, H., Yue, L.Q., Hong, E.G., et al. Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice. Am. J. Physiol. Endocrinol. Metab. 294 (2008), E261–E270.
98. Lee, C., Zeng, J., Drew, B.G., Sallam, T., Martin-Montalvo, A., Wan, J., et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 21 (2015), 443–454.
99. Levian, C., Ruiz, E., Yang, X., The pathogenesis of obesity from a genomic and systems biology perspective. Yale J. Biol. Med. 87 (2014), 113–126.
100. Li, Y., He, Y., Qi, L., Jaddoe, V.W., Feskens, E.J., Yang, X., et al. Exposure to the Chinese famine in early life and the risk of hyperglycemia and type 2 diabetes in adulthood. Diabetes 59 (2010), 2400–2406.
101. Ling, C., Poulsen, P., Simonsson, S., Rönn, T., Holmkvist, J., Almgren, P., et al. Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle. J. Clin. Investig. 117 (2007), 3427–3435.
102. Lips, M.A., Van Klinken, J.B., van Harmelen, V., Dharuri, H.K., Hoen, P.A., Laros, J.F., et al. Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes. Diabetes Care 37 (2014), 3150–3156.
103. Liu, C., Wu, J., Zhu, J., Kuei, C., Yu, J., Shelton, J., et al. Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81. J. Biol. Chem. 284 (2009), 2811–2822.
104. Locasale, J.W., Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer 13 (2013), 572–583.
105. Lopes, T.I., Geloneze, B., Pareja, J.C., Calixto, A.R., Ferreira, M.M., Marsaioli, A.J., Blood metaboloma changes before and after bariatric surgery: a (1)H NMR-based clinical investigation. OMICS 19 (2015), 318–327.
106. Lopes, T.I., Geloneze, B., Pareja, J.C., Calixto, A.R., Ferreira, M.M., Marsaioli, A.J., “Omics” prospective monitoring of bariatric surgery: Roux-en-Y gastric bypass outcomes using mixed-meal tolerance test and time-resolved (1)H NMR-based metabolomics. OMICS 20 (2016), 415–423.
107. Louie, K., Minor, A., Ng, R., Poon, K., Chow, V., Ma, S., Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligoospermic men in association with MTHFR C677T genotype. Andrology, 2016, 10.1111/andr.12240.
108. Maddocks, O.D., Labuschagne, C.F., Adams, P.D., Vousden, K.H., Serine metabolism supports the methionine cycle and DNA/RNA methylation through De Novo ATP synthesis in Cancer cells. Mol. Cell. 61 (2016), 210–221.
109. Mägi, R., Manning, S., Yousseif, A., Pucci, A., Santini, F., Karra, E., et al. Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery. PLoS One, 8(8), 2013, e70735.
110. Marchi, M., Lisi, S., Curcio, M., Barbuti, S., Piaggi, P., Ceccarini, G., et al. Human leptin tissue distribution, but not weight loss-dependent change in expression, is associated with methylation of its promoter. Epigenetics 6 (2011), 1198–1206.
111. Martinez-Hervas, S., Argente, C., Garcia-Jodar, J., Priego, A., Real, J.T., Carratala, A., et al. Misclassification of subjects with insulin resistance and associated cardiovascular risk factors by homeostasis model assessment index. Utility of a postprandial method based on oral glucose tolerance test. Metabolism 60 (2011), 740–746.
112. Martinez-Outschoorn, U.E., Peiris-Pagés, M., Pestell, R.G., Sotgia, F., Lisanti, M.P., Cancer metabolism: a therapeutic perspective. Nat. Rev. Clin. Oncol., 2016, 10.1038/nrclinonc.2016.60.
113. Masana, L., Camprubi, M., Sarda, P., Sola, R., Joven, J., Turner, P.R., The Mediterranean-type diet: is there a need for further modification?. Am. J. Clin. Nutr. 1991:53 (1991), 886–889.
114. Matzko, M.E., Argyropoulos, G., Wood, G.C., Chu, X., McCarter, R.J., Still, C.D., et al. Association of ghrelin receptor promoter polymorphisms with weight loss following Roux-en-Y gastric bypass surgery. Obes. Surg. 22 (2012), 783–790.
115. Menendez, J.A., Joven, J., Energy metabolism and metabolic sensors in stem cells: the metabostem crossroads of aging and cancer. Adv. Exp. Med. Biol. 824 (2014), 117–140.
116. Menendez, J.A., Quirantes-Piné, R., Rodríguez-Gallego, E., Cufí, S., Corominas-Faja, B., Cuyàs, E., et al. Oncobiguanides: paracelsus' law and nonconventional routes for administering diabetobiguanides for cancer treatment. Oncotarget 5 (2014), 2344–2348.
117. Menendez, J.A., Corominas-Faja, B., Cuyàs, E., García, M.G., Fernández- Arroyo, S., Fernández, A.F., et al. Oncometabolic nuclear reprogramming of Cancer stemness. Stem Cell Rep. 6 (2016), 273–283.
118. Menendez, J.A., Folguera-Blasco, N., Cuyàs, E., Fernández-Arroyo, S., Joven, J., Alarcón, T., Accelerated geroncogenesis in hereditary breast- ovarian cancer syndrome. Oncotarget 7 (2016), 11959–11971.
119. Menotti, A., The European multifactorial preventive trial of coronary heart disease: four-year experience. Prev. Med. 12 (1983), 175–180.
120. Mentch, S.J., Locasale, J.W., One-carbon metabolism and epigenetics: understanding the specificity. Ann. N.Y. Acad. Sci. 1363 (2016), 91–98.
121. Mentch, S.J., Mehrmohamadi, M., Huang, L., Liu, X., Gupta, D., Mattocks, D., et al. Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism. Cell Metab. 22 (2015), 861–873.
122. Moore, B.S., Mirshahi, U.L., Yost, E.A., Stepanchick, A.N., Bedrin, M.D., Styer, A.M., et al. Long-term weight-loss in gastric bypass patients carrying melanocortin 4 receptor variants. PLoS One, 9, 2014, 10.1371/journal.pone.0093629.
123. Morton, N.M., Densmore, V., Wamil, M., Ramage, L., Nichol, K., Bünger, L., et al. A polygenic model of the metabolic syndrome with reduced circulating and intra-adipose glucocorticoid action. Diabetes 54 (2005), 3371–3378.
124. Morton, N.M., Beltram, J., Carter, R.N., Michailidou, Z., Gorjanc, G., McFadden, C., et al. Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness. Nat. Med., 2016, 10.1038/nm.4115.
125. Mutch, D.M., Furhmann, J.C., Rein, D., Wiemer, J.C., Bouillot, J.L., Poitou, C., et al. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery. PLoS One, 19, 2009, 10.1371/journal.pone.0007905.
126. NCD Risk Factor Collaboration (502 authors), Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants. Lancet 387 (2016), 1513–1530.
127. Nicholson, J.K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., et al. Host-gut microbiota metabolic interactions. Science 336 (2012), 1262–1267.
128. Nilsson, E., Jansson, P.A., Perfilyev, A., Volkov, P., Pedersen, M., Svensson, M.K., et al. Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes 63 (2014), 2962–2976.
129. Nilsson, E., Matte, A., Perfilyev, A., de Mello, V.D., Käkelä, P., Pihlajamäki, J., et al. Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels. J. Clin. Endocrinol. Metab. 100 (2015), E1491–E1501.
130. Noureen, N., Touseef, M., Fazal, S., Qadir, M.A., ChromClust: a semi- supervised chromatin clustering toolkit for mining histone modifications interplay. Genomics 106 (2015), 355–359.
131. Novère, N., Quantitative and logic modelling of molecular and gene networks. Nat. Rev. Genet. 16 (2015), 146–158.
132. Orentreich, N., Matias, J.R., DeFelice, A., Zimmerman, J.A., Low methionine ingestion by rats extends life span. J. Nutr. 123 (1993), 269–274.
133. Orgeron, M.L., Stone, K.P., Wanders, D., Cortez, C.C., Van, N.T., Gettys, T.W., The impact of dietary methionine restriction on biomarkers of metabolic health. Glucose Homeost. Pathog. Diabetes Mellit. 121 (2014), 351–376.
134. Öst, A., Lempradl, A., Casas, E., Weigert, M., Tiko, T., Deniz, M., et al. Paternal diet defines offspring chromatin state and intergenerational obesity. Cell 159 (2014), 1352–1364.
135. Painter, R.C., Roseboom, T.J., Bleker, O.P., Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod. Toxicol. 20 (2005), 345–352.
136. Patti, M.E., Intergenerational programming of metabolic disease: evidence from human populations and experimental animal models. Cell Mol. Life. Sci. 70 (2013), 1597–1608.
137. Pisprasert, V., Ingram, K.H., Lopez-Davila, M.F., Munoz, A.J., Garvey, W.T., Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans. Diabetes Care 36 (2013), 845–853.
138. Preussner, J., Bayer, J., Kuenne, C., Looso, M., ADMIRE: analysis and visualization of differential methylation in genomic regions using the Infinium HumanMethylation450 Assay. Epigenet. Chromatin, 8, 2015, 51.
139. Puig-Costa, M., Codina-Cazador, A., Cortés-Pastoret, E., Oliveras-Ferraros, C., Cufí, S., Flaquer, S., et al. Discovery and validation of an INflammatory PROtein-driven GAstric cancer Signature (INPROGAS) using antibody microarray-based oncoproteomics. Oncotarget 5 (2014), 1942–1954.
140. Raghavan, R.P., Laight, D.W., Cummings, M.H., Aspirin in type 2 diabetes, a randomised controlled study: effect of different doses on inflammation, oxidative stress, insulin resistance and endothelial function. Int. J. Clin. Pract. 68 (2014), 271–277.
141. Riera-Borrull, M., Rodríguez-Gallego, E., Hernández-Aguilera, A., Luciano, F., Ras, R., Cuyàs, E., et al. Exploring the process of energy generation in pathophysiology by targeted metabolomics: performance of a simple and quantitative method. J. Am. Soc. Mass. Spectrom. 27 (2016), 168–177.
142. Rodrigues, G.K., Resende, C.M., Durso, D.F., Rodrigues, L.A., Silva, J.L., Reis, R.C., et al. A single FTO gene variant rs9939609 is associated with body weight evolution in a multiethnic extremely obese population that underwent bariatric surgery. Nutrition 31 (2015), 1344–1350.
143. Rodríguez-Gallego, E., Guirro, M., Riera-Borrull, M., Hernández-Aguilera, A., Mariné-Casadó, R., Fernández-Arroyo, S., et al. Mapping of the circulating metabolome reveals α-ketoglutarate as a predictor of morbid obesity-associated non-alcoholic fatty liver disease. Int. J. Obes. (Lond) 39 (2015), 279–287.
144. Rönn, T., Ling, C., DNA methylation as a diagnostic and therapeutic target in the battle against Type 2 diabetes. Epigenomics 7 (2015), 451–460.
145. Roy, M., Reddy, P.H., Iijima, M., Sesaki, H., Mitochondrial division and fusion in metabolism. Curr. Opin. Cell. Biol. 33 (2015), 111–118.
146. Rull, A., Rodríguez, F., Aragonès, G., Marsillach, J., Beltrán, R., Alonso- Villaverde, C., et al. Hepatic monocyte chemoattractant protein-1 is upregulated by dietary cholesterol and contributes to liver steatosis. Cytokine 48 (2009), 273–279.
147. Rull, A., Geeraert, B., Aragonès, G., Beltrán-Debón, R., Rodríguez-Gallego, E., García-Heredia, A., et al. Rosiglitazone and fenofibrate exacerbate liver steatosis in a mouse model of obesity and hyperlipidemia. A transcriptomic and metabolomic study. J. Proteome Res. 13 (2014), 1731–1743.
148. Sacks, F.M., Bray, G.A., Carey, V.J., Smith, S.R., Ryan, D.H., Anton, S.D., et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N. Engl. J. Med. Feb 26 (2009), 859–873.
149. Sarparanta, J., García-Macia, M., Singh, R., Autophagy and mitochondria in obesity and type 2 diabetes. Curr. Diabetes Rev., 12, 2016 2016 Feb 17.
150. Sena, L.A., Chandel, N.S., Physiological roles of mitochondrial reactive oxygen species. Mol. Cell. 48 (2012), 158–167.
151. Sethe, S., Scutt, A., Stolzing, A., Aging of mesenchymal stem cells. Ageing Res. Rev. 5 (2006), 91–116.
152. Shai, I., Schwarzfuchs, D., Henkin, Y., Shahar, D.R., Witkow, S., Greenberg, I., et al., Dietary Intervention Randomized Controlled Trial (DIRECT) Group, Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N. Engl. J. Med. 359 (2008), 229–241.
153. Shaw, R.J., Metformin trims fats to restore insulin sensitivity. Nat. Med. 19 (2013), 1570–1572.
154. Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339 (2013), 211–214.
155. Shyh-Chang, N., Locasale, J.W., Lyssiotis, C.A., Zheng, Y., Teo, R.Y., Ratanasirintrawoot, S., et al. Influence of threonine metabolism on S-adenosylmethionine and histone methylation. Science 339 (2013), 222–226.
156. Siklenka, K., Erkek, S., Godmann, M., Lambrot, R., McGraw, S., Lafleur, C., et al. Disruption of histone methylation in developing sperm impairs offspring health transgenerationally. Science, 350(6261), 2015 aab2006.
157. Solomon, D.H., Massarotti, E., Garg, R., Liu, J., Canning, C., Schneeweiss, S., Association between disease-modifying antirheumatic drugs and diabetes risk in patients with rheumatoid arthritis and psoriasis. J. Am. Med. Assoc. 305 (2011), 2525–2531.
158. Stanley, T.L., Zanni, M.V., Johnsen, S., Rasheed, S., Makimura, H., Lee, H., et al. TNF-a antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J. Clin. Endocrinol. Metab. 96 (2011), E146–E150.
159. Stanner, S.A., Bulmer, K., Andrès, C., Lantseva, O.E., Borodina, V., Poteen, V.V., Yudkin, J.S., Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study. BMJ 315 (1997), 1342–1348.
160. Su, S., Liu, Q., Chen, J., Chen, J., Chen, F., He, C., et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 25 (2014), 605–620.
161. Suliman, H.B., Piantadosi, C.A., Mitochondrial quality control as a therapeutic target. Pharmacol. Rev. 68 (2016), 20–48.
162. Takahashi, K., Yamanaka, S., Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 (2006), 663–676.
163. Tang, W.W., Dietmann, S., Irie, N., Leitch, H.G., Floros, V.I., Bradshaw, C.R., et al. A unique gene regulatory network resets the human germline epigenome for development. Cell 161 (2015), 1453–1467.
164. Tannahill, G.M., Curtis, A.M., Adamik, J., Palsson-McDermott, E.M., McGettrick, A.F., Goel, G., et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496 (2013), 238–242.
165. Tate, P.H., Bird, A.P., Effects of DNA methylation on DNA-binding proteins and gene expression. Curr. Opin. Genet. Dev. 3 (1993), 226–231.
166. Tateishi, K., Okada, Y., Kallin, E.M., Zhang, Y., Role of Jhdm2a in regulating metabolic gene expression and obesity resistance. Nature 458 (2009), 757–761.
167. Tobi, E.W., Goeman, J.J., Monajemi, R., Gu, H., Putter, H., Zhang, Y., et al. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat. Commun., 5, 2014, 5592.
168. Toperoff, G., Aran, D., Kark, J.D., Rosenberg, M., Dubnikov, T., Nissan, B., et al. Genome-wide survey reveals predisposing diabetes type 2- related DNA methylation variations in human peripheral blood. Hum. Mol. Genet. 21 (2012), 371–383.
169. Twig, G., Yaniv, G., Levine, H., Leiba, A., Goldberger, N., Derazne, E., et al. Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. N. Engl. J. Med. 374 (2016), 2430–2440.
170. van Asseldonk, E.J.P., Stienstra, R., Koenen, T.B., Joosten, L.A.B., Netea, M.G., Tack, C.J., Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study. J. Clin. Endocrinol. Metab. 96 (2011), 2119–2126.
171. van den Dungen, M.W., Murk, A.J., Kok, D.E., Steegenga, W.T., Comprehensive DNA methylation and gene expression profiling in differentiating human adipocytes. J. Cell Biochem., 2016, 10.1002/jcb.25568.
172. van Dijk, S.J., Molloy, P.L., Varinli, H., Morrison, J.L., Muhlhausler, B.S., Epigenetics and human obesity. Int. J. Obes. (Lond) 39 (2015), 85–97.
173. Vazquez-Martin, A., van den Haute, C., Cufi, S., Corominas, B., Cuyas, E., Lopez-Bonet, E., et al. Mitophagy-driven mitochondrial rejuvenation regulates stem cell fate. Aging 8 (2016), 1330–1352.
174. Waterland, R.A., Dolinoy, D.C., Lin, J.R., Smith, C.A., Shi, X., Tahiliani, K.G., Maternal methyl supplements increase offspring DNA methylation at Axin Fused. Genesis 44 (2006), 401–406.
175. Weaver, I.C., Champagne, F.A., Brown, S.E., Dymov, S., Sharma, S., Meaney, M.J., et al. Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J. Neurosci. 25 (2005), 11045–11054.
176. Wei, Y., Chen, Y.H., Li, L.Y., Lang, J., Yeh, S.P., Shi, B., et al. CDK1- dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nat. Cell Biol. 13 (2011), 87–94.
177. Wellen, K.E., Thompson, C.B., A two-way street: reciprocal regulation of metabolism and signalling. Nat. Rev. Mol. Cell Biol. 13 (2012), 270–276.
178. Woo, D.K., Shadel, G.S., Mitochondrial stress signals revise an old aging theory. Cell 144 (2011), 11–12.
179. Zaccardi, F., Webb, D.R., Yates, T., Davies, M.J., Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad. Med. J. 92 (2016), 63–69.
180. Zaccardi, F., Htike, Z.Z., Webb, D.R., Khunti, K., Davies, M.J., Benefits and harms of once-weekly glucagon-like Peptide-1 receptor agonist treatments: a systematic review and network meta-analysis. Ann. Intern. Med. 164 (2016), 102–113.