K. Achiwa, M. Ishigami, Y. Ishizu, T. Kuzuya, T. Honda et al., DSS Colitis Promotes Tumorigenesis and Fibrogenesis in a Choline-Deficient High-Fat Diet-Induced NASH Mouse Model, vol.470, pp.15-21, 2016.

E. Aigner, I. Theurl, H. Haufe, M. Seifert, F. Hohla et al., Copper Availability Contributes to Iron Perturbations in Human Nonalcoholic Fatty Liver Disease, vol.135, pp.680-88, 2008.

E. Aigner, G. Weiss, C. Et, and . Datz, « Dysregulation of Iron and Copper Homeostasis in Nonalcoholic Fatty Liver, World Journal of Hepatology, vol.7, issue.2, pp.177-88, 2015.

S. Akbulut, E. Altiparmak, F. Topal, and E. Ozaslan, Metin Kucukazman, et Ozlem Yonem. 2010. « Increased Levels of Homocysteine in Patients with Ulcerative Colitis, World Journal of Gastroenterology, vol.16, pp.2411-2427

N. Akchiche, C. Bossenmeyer-pourié, R. Kerek, N. Martin, G. Pourié et al., Homocysteinylation of Neuronal Proteins Contributes to Folate Deficiency-Associated Alterations of Differentiation, Vesicular Transport, and Plasticity in Hippocampal Neuronal Cells, vol.26, pp.3980-92, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00759122

O. S. Al-attas, M. Nasser, K. Al-daghri, N. F. Al-rubeaan, S. L. Da-silva et al., Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies, vol.8, p.20, 2009.

A. Alisi, M. Manco, R. Devito, F. Piemonte, and . Et-valerio-nobili, Endotoxin and Plasminogen Activator Inhibitor-1 Serum Levels Associated with Nonalcoholic Steatohepatitis in Children, vol.50, pp.645-694, 2010.

. Al-rasadi, M. Khalid, G. Rizzo, . Montalto, G. Et et al., Nonalcoholic Fatty Liver Disease, Cardiovascular Risk, and Carotid Inflammation, vol.66, pp.601-604, 2015.

J. Amar, R. Burcelin, J. Bernard-ruidavets, P. D. Cani, J. Fauvel et al., Energy Intake Is Associated with Endotoxemia in Apparently Healthy Men, vol.87, pp.1219-1242, 2008.

Q. M. Anstee, C. P. Et, and . Day, « The Genetics of NAFLD », Nature Reviews. Gastroenterology & Hepatology, vol.10, issue.11, pp.645-55, 2013.

,

A. C. Antony, « In Utero Physiology: Role of Folic Acid in Nutrient Delivery and Fetal Development, The American Journal of Clinical Nutrition, vol.85, issue.2, pp.598-603, 2007.

J. Araya, R. Rodrigo, L. A. Videla, L. Thielemann, M. Orellana et al., « Increase in Long-Chain Polyunsaturated Fatty Acid n -6/n -3 Ratio in Relation to Hepatic Steatosis in Patients with Non-Alcoholic Fatty Liver Disease, Clinical Science, vol.106, issue.6, pp.635-678, 1979.

L. Arisqueta, M. Nuñez-garcia, J. Ogando, I. Garcia-arcos, B. Ochoa et al., Olatz Fresnedo, et Yuri Rueda. 2013. « Involvement of Lipid Droplets in Hepatic Responses to Lipopolysaccharide Treatment in Mice, Biochimica et Biophysica Acta (BBA) -Molecular and Cell Biology of Lipids, vol.1831, issue.8, pp.1357-67

A. Asgharpour, S. C. Cazanave, T. Pacana, M. Seneshaw, R. Vincent et al., « A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer, Journal of hepatology, vol.65, issue.3, pp.579-88, 2016.

F. Bäckhed, H. Ding, T. Wang, L. V. Hooper, G. Y. Koh et al., « The Gut Microbiota as an Environmental Factor That Regulates Fat Storage, Proceedings of the National Academy of Sciences of the United States of America, vol.101, issue.44, pp.15718-15741, 2004.

B. R. Bacon, M. J. Farahvash, C. G. Janney, and B. A. Neuschwander-tetri, « Nonalcoholic Steatohepatitis: An Expanded Clinical Entity, Gastroenterology, vol.107, issue.4, pp.1103-1112, 1994.

C. Baeck, A. Wehr, F. Karlin-raja-karlmark, M. Heymann, N. Vucur et al., « Pharmacological Inhibition of the Chemokine CCL2 (MCP-1) Diminishes Liver Macrophage Infiltration and Steatohepatitis in Chronic Hepatic Injury, Gut, vol.61, issue.3, pp.416-442, 2012.

D. Barker and . Osmond, « Diet and coronary heart disease in England and Wales during and after the second world war, Journal of Epidemiology and Community Health, vol.40, issue.1, pp.37-44, 1986.

D. J. Barker and C. Osmond, « Infant Mortality, Childhood Nutrition, and Ischaemic Heart Disease in England and Wales, Lancet, vol.1, issue.8489, pp.1077-81, 1986.

S. Barquera, L. Hernandez-barrera, M. L. Tolentino, J. Espinosa, S. W. Ng et al., Energy Intake from Beverages Is Increasing among Mexican Adolescents and Adults, vol.138, pp.2454-61, 2008.

. Battaglia-hsu, N. Shyue-fang, N. Akchiche, J. Noel, E. Alberto et al., « Vitamin B12 Deficiency Reduces Proliferation and Promotes Differentiation of Neuroblastoma Cells and Up-Regulates PP2A, ProNGF, and TACE, Proceedings of the National Academy of Sciences of the United States of America, vol.106, issue.51, pp.21930-21965, 2009.

M. Baumgart, B. Dogan, M. Rishniw, G. Weitzman, B. Bosworth et al., « Culture Independent Analysis of Ileal Mucosa Reveals a Selective Increase in Invasive Escherichia Coli of Novel Phylogeny Relative to Depletion of Clostridiales in Crohn's Disease Involving the Ileum, The ISME Journal, vol.1, issue.5, pp.403-421, 2007.

C. Becker, M. C. Fantini, S. Wirtz, A. Nikolaev, R. Kiesslich et al., « In Vivo Imaging of Colitis and Colon Cancer Development in Mice Using High Resolution Chromoendoscopy, Gut, vol.54, issue.7, pp.950-54, 2005.

,

P. Bedossa, « Pathology of Non-Alcoholic Fatty Liver Disease, Liver International: Official Journal of the International Association for the Study of the Liver, vol.37, pp.85-89, 2017.

K. Begriche, A. Igoudjil, D. Pessayre, B. Et, and . Fromenty, « Mitochondrial Dysfunction in NASH: Causes, Consequences and Possible Means to, Prevent It ». Mitochondrion, vol.6, issue.1, pp.1-28, 2006.

E. L. Bell, S. Et-navdeep, and . Chandel, « Genetics of Mitochondrial Electron Transport Chain in Regulating Oxygen Sensing, Methods in Enzymology, vol.435, pp.447-61, 2007.

B. Benoist and . De, « Conclusions of a WHO Technical Consultation on Folate and Vitamin B12 Deficiencies, Food and Nutrition Bulletin, vol.29, issue.2_suppl1, pp.238-282, 2008.

R. D. Berg, « The indigenous gastrointestinal microflora, Trends in Microbiology, vol.4, issue.11, pp.10057-10060, 1996.

C. N. Bernstein and A. Et, « Hospitalization, Surgery, and Readmission Rates of IBD in Canada: A Population-Based Study, The American Journal of Gastroenterology, vol.101, issue.1, pp.110-128, 2006.

T. Bessissow, N. H. Le, K. Rollet, W. Afif, A. Bitton et al., « Incidence and Predictors of Nonalcoholic Fatty Liver Disease by Serum Biomarkers in Patients with Inflammatory Bowel Disease, Inflammatory Bowel Diseases, vol.22, issue.8, pp.1937-1981, 2016.

K. Bettermann, T. Hohensee, J. Et, and . Haybaeck, « Steatosis and Steatohepatitis: Complex Disorders, International Journal of Molecular Sciences, vol.15, issue.6, pp.9924-9968, 2014.

A. L. Birkenfeld, G. I. Et, and . Shulman, « Nonalcoholic Fatty Liver Disease, Hepatic Insulin Resistance, and Type 2 Diabetes, Hepatology, vol.59, issue.2, pp.713-736, 2014.

A. Bison, A. Marchal-bressenot, Z. Li, I. Elamouri, E. Feigerlova et al., « Foetal Programming by Methyl Donor Deficiency Produces Steato-Hepatitis in Rats Exposed to High Fat Diet, Scientific Reports, vol.6, p.37207, 2016.

S. A. Blaise, E. Nédélec, J. Alberto, H. Schroeder, S. Audonnet et al., « Short Hypoxia Could Attenuate the Adverse Effects of Hyperhomocysteinemia on the Developing Rat Brain by Inducing Neurogenesis », Experimental Neurology, vol.216, issue.1, pp.231-269, 2009.

S. A. Blaise, E. Nédélec, H. Schroeder, J. Alberto, C. Bossenmeyer-pourié et al., « Gestational Vitamin B Deficiency Leads to Homocysteine-Associated Brain Apoptosis and Alters Neurobehavioral Development in Rats, The American Journal of Pathology, vol.170, issue.2, pp.667-79, 2007.

S. Blaise, J. Alberto, E. Nédélec, A. Ayav, G. Pourié et al., « Mild Neonatal Hypoxia Exacerbates the Effects of Vitamin-Deficient Diet on Homocysteine Metabolism in Rats, Pediatric Research, vol.57, issue.6, pp.777-82, 2005.

,

H. J. Blom, Y. Et, and . Smulders, With Special References to Cardiovascular Disease and Neural Tube Defects », Journal of Inherited Metabolic Disease, vol.34, issue.1, pp.75-81, 2011.

C. Bocca, E. Novo, A. Miglietta, M. Et, and . Parola, Angiogenesis and Fibrogenesis in Chronic Liver Diseases, vol.1, pp.477-88, 2015.

S. Bogaert, M. D. Vos, K. Olievier, H. Peeters, D. Elewaut et al., « Involvement of Endoplasmic Reticulum Stress in Inflammatory Bowel Disease: A Different Implication for Colonic and Ileal Disease?, PloS One, vol.6, issue.10, p.25589, 2011.

C. Bossenmeyer-pourié, S. Blaise, G. Pourié, C. Tomasetto, S. Audonnet et al., « Methyl Donor Deficiency Affects Fetal Programming of Gastric Ghrelin Cell Organization and Function in the Rat, The American Journal of Pathology, vol.176, issue.1, pp.270-77, 2010.

C. Bossenmeyer-pourié, G. Pourié, V. Koziel, D. Helle, E. Jeannesson et al., « Early Methyl Donor Deficiency Produces Severe Gastritis in Mothers and Offspring through N-Homocysteinylation of Cytoskeleton Proteins, Cellular Stress, and Inflammation, FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, vol.27, issue.6, pp.2185-97, 2013.

T. Bottiglieri, « Homocysteine and Folate Metabolism in Depression », Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol.29, issue.7, pp.1103-1115, 2005.

J. Boursier, O. Mueller, M. Barret, M. Machado, L. Fizanne et al., « The severity of NAFLD is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota, Hepatology, vol.63, issue.3, pp.764-75, 2016.

G. A. Bray, B. M. Samara-joy-nielsen, and . Popkin, « Consumption of HighFructose Corn Syrup in Beverages May Play a Role in the Epidemic of Obesity, The American Journal of Clinical Nutrition, vol.79, issue.4, pp.537-580, 2004.

A. Bressenot, S. Pooya, C. Bossenmeyer-pourie, G. Gauchotte, A. Germain et al., « Methyl Donor Deficiency Affects SmallIntestinal Differentiation and Barrier Function in Rats, British Journal of Nutrition, vol.109, issue.04, pp.667-77, 2013.

P. Brun, I. Castagliuolo, V. D. Leo, A. Buda, M. Pinzani et al., « Increased Intestinal Permeability in Obese Mice: New Evidence in the Pathogenesis of Nonalcoholic Steatohepatitis, American Journal of Physiology-Gastrointestinal and Liver Physiology, vol.292, issue.2, pp.518-543, 2007.

,

E. M. Brunt, C. G. Janney, A. M. Di-bisceglie, B. A. Neuschwander-tetri, and B. R. Bacon,

S. «-nonalcoholic, A Proposal for Grading and Staging the Histological Lesions, The American Journal of Gastroenterology, vol.94, issue.9, pp.2467-74

E. M. Brunt, W. Vincent, V. Wong, C. P. Nobili, S. Day et al., Nonalcoholic Fatty Liver Disease, 2015.

E. Bugianesi, S. Moscatiello, M. F. Ciaravella, and G. Marchesini, « Insulin Resistance in Nonalcoholic Fatty Liver Disease, Current Pharmaceutical Design, vol.16, issue.17, pp.1941-51, 2010.

E. Bugianesi, N. Leone, E. Vanni, G. Marchesini, F. Brunello et al., Expanding the Natural History of Nonalcoholic Steatohepatitis: From Cryptogenic Cirrhosis to Hepatocellular Carcinoma, Gastroenterology, vol.123, issue.1, pp.134-174, 2002.

E. Buzzetti, M. Pinzani, E. A. Et, and . Tsochatzis, « The Multiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD), Metabolism, vol.65, issue.8, pp.1038-1086, 2016.

F. Caballero, A. Fernández, N. Matías, L. Martínez, R. Fucho et al., Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis: Impact on Mitochondrial S-Adenosyl-L-Methionine and Glutathione, vol.285, pp.18528-18564, 2010.

S. H. Caldwell, D. H. Oelsner, J. C. Iezzoni, E. E. Hespenheide, E. H. Battle et al.,

C. «-cryptogenic, Clinical Characterization and Risk Factors for Underlying Disease, Hepatology, vol.29, issue.3, pp.664-69

,

P. D. Cani, J. Amar, M. A. Iglesias, M. Poggi, C. Knauf et al., Metabolic Endotoxemia Initiates Obesity and Insulin Resistance, vol.56, pp.1761-72, 2007.

P. D. Cani, R. Bibiloni, C. Knauf, A. Waget, A. M. Neyrinck et al., « Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice, Diabetes, vol.57, issue.6, pp.1470-81, 2008.

C. Cantó and J. Auwerx, « PGC-1alpha, SIRT1 and AMPK, an Energy Sensing Network That Controls Energy Expenditure, Current Opinion in Lipidology, vol.20, issue.2, pp.98-105, 2009.

C. Cantó and J. Auwerx, « Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD(+)?, Pharmacological Reviews, vol.64, issue.1, pp.166-87, 2012.

,

S. Carotti, U. Vespasiani-gentilucci, G. Perrone, A. Picardi, S. Et et al., « Portal Inflammation during NAFLD Is Frequent and Associated with the Early Phases of Putative Hepatic Progenitor Cell Activation, Journal of Clinical Pathology, vol.68, issue.11, pp.883-90, 2015.

D. Ceccarelli, D. Gallesi, F. Giovannini, M. Ferrali, and A. Masini, « Relationship between Free Iron Level and Rat Liver Mitochondrial Dysfunction in Experimental Dietary Iron Overload, Biochemical and Biophysical Research Communications, vol.209, issue.1, pp.53-59, 1995.

N. S. Chandel, E. Maltepe, E. Goldwasser, C. E. Mathieu, M. C. Simon et al.,

. «-mitochondrial-reactive, Oxygen Species Trigger Hypoxia-Induced Transcription, Proceedings of the National Academy of Sciences of the United States of America, vol.95, pp.11715-11735

M. Chen, L. Peyrin-biroulet, A. George, F. Coste, A. Bressenot et al., « Methyl Deficient Diet Aggravates Experimental Colitis in Rats, Journal of Cellular and Molecular Medicine, vol.15, issue.11, pp.2486-97, 2011.

D. Coelho, T. Suormala, M. Stucki, J. P. Lerner-ellis, D. S. Rosenblatt et al., Gene Identification for the cblD Defect of Vitamin B 12 Metabolism, N. Engl. J. Med, vol.358, pp.1454-1464, 2008.

L. Conterno, F. Fava, R. Viola, M. Et-kieran, and . Tuohy, « Obesity and the Gut Microbiota: Does up-Regulating Colonic Fermentation Protect against Obesity and Metabolic Disease?, Genes & Nutrition, vol.6, issue.3, pp.241-60, 2011.

K. D. Corbin, H. Et-steven, and . Zeisel, « Choline Metabolism Provides Novel Insights into Non-alcoholic Fatty Liver Disease and its Progression, Current opinion in gastroenterology, vol.28, issue.2, pp.159-65, 2012.

A. Coste, J. Louet, M. Lagouge, C. Lerin, M. C. Antal et al.,

, The Genetic Ablation of SRC-3 Protects against Obesity and Improves Insulin Sensitivity by Reducing the Acetylation of PGC-1{alpha}, Proceedings of the National Academy of Sciences of the United States of America, vol.105, pp.17187-92

R. Crescenzo, F. Bianco, I. Falcone, P. Coppola, G. Liverini et al., « Increased Hepatic de Novo Lipogenesis and Mitochondrial Efficiency in a Model of Obesity Induced by Diets Rich in Fructose, European Journal of Nutrition, vol.52, issue.2, pp.537-582, 2013.

T. Csak, M. Ganz, J. Pespisa, K. Kodys, A. Dolganiuc et al., « Fatty Acid and Endotoxin Activate Inflammasomes in Mouse Hepatocytes that Release Danger Signals to Stimulate Immune Cells, Hepatology, vol.54, issue.1, pp.133-177, 2011.

X. Cui, Y. Jin, A. B. Hofseth, E. Pena, J. Habiger et al., « Resveratrol Suppresses Colitis and Colon Cancer Associated with Colitis, Cancer Prevention Research, vol.3, issue.4, pp.549-59, 2010.

S. Danese, A. Sgambato, A. Papa, F. Scaldaferri, R. Pola et al.,

, « Homocysteine Triggers Mucosal Microvascular Activation in Inflammatory Bowel Disease, vol.100, pp.886-95

J. Daval, S. Blaise, and J. Guéant, « Vitamin B Deficiency Causes Neural Cell Loss and Cognitive Impairment in the Developing Rat, Proceedings of the National Academy of Sciences of the United States of America, vol.106, 2009.

P. D. Delzenne and N. M. Cani, « The Role of the Gut Microbiota in Energy Metabolism and Metabolic Disease, Current Pharmaceutical Design. 1 mai, 2009.

S. L. Deshmane, S. Sergey-kremlev, . Amini, B. E. Et, and . Sawaya, « Monocyte Chemoattractant Protein-1 (MCP-1): An Overview », Journal of Interferon & Cytokine Research, vol.29, issue.6, pp.313-339, 2009.

L. J. Dixon, C. A. Flask, B. G. Papouchado, A. E. Feldstein, and L. E. Nagy, « Caspase-1 as a Central Regulator of High Fat Diet-Induced Non-Alcoholic Steatohepatitis », PLoS ONE, vol.8, issue.2, 2013.

S. J. Dixon, B. R. Et, and . Stockwell, « The Role of Iron and Reactive Oxygen Species in Cell Death », Nature Chemical Biology, vol.10, issue.1, pp.9-17, 2014.

,

P. Dongiovanni, S. Romeo, L. Et, and . Valenti, Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis, p.460190, 2015.

K. L. Donnelly, I. Coleman, S. J. Smith, J. Schwarzenberg, . Jessurun et al.,

E. J. Boldt and . Parks, « Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease, Journal of Clinical Investigation, vol.115, issue.5, pp.1343-51, 2005.

K. J. Dudley, M. Deborah, K. L. Sloboda, J. Connor, . Beltrand et al., Offspring of Mothers Fed a High Fat Diet Display Hepatic Cell Cycle Inhibition and Associated Changes in Gene Expression and DNA Methylation, PloS One, vol.6, issue.7, p.21662, 2011.

K. J. Duffey, B. M. Et, and . Popkin, « Shifts in Patterns and Consumption of Beverages between, Obesity (Silver Spring, Md.), vol.15, issue.11, pp.2739-2786, 1965.

C. Erridge, T. Attina, C. M. Spickett, and D. J. Webb, « A High-Fat Meal Induces Low-Grade Endotoxemia: Evidence of a Novel Mechanism of Postprandial Inflammation, The American Journal of Clinical Nutrition, vol.86, issue.5, pp.1286-92, 2007.

A. Farhadi, S. Gundlapalli, M. Shaikh, C. Frantzides, L. Harrell et al., « Susceptibility to Gut Leakiness: A Possible Mechanism for Endotoxaemia in Non-Alcoholic Steatohepatitis, Liver International: Official Journal of the International Association for the Study of the Liver, vol.28, issue.7, pp.1026-1059, 2008.

G. C. Farrell, F. Haczeyni, S. Et, and . Chitturi, « Pathogenesis of NASH: How Metabolic Complications of Overnutrition Favour Lipotoxicity and ProInflammatory Fatty Liver Disease, Obesity, Fatty Liver and Liver Cancer, pp.19-44, 2018.

W. A. Faubion, E. V. Loftus, W. J. Sandborn, D. K. Freese, and J. Perrault, « Pediatric "PSC-IBD": A Descriptive Report of Associated Inflammatory Bowel Disease among Pediatric Patients with Psc, Journal of Pediatric Gastroenterology and Nutrition, vol.33, issue.3, pp.296-300, 2001.

. Forges, P. Thierry, J. M. Monnier-barbarino, R. M. Alberto, J. L. Guéant-rodriguez et al., « Impact of Folate and Homocysteine Metabolism on Human Reproductive Health, Human Reproduction Update, vol.13, issue.3, pp.225-263, 2007.

,

T. H. Frazier, A. M. Stocker, N. A. Kershner, L. S. Marsano, and J. Craig,

. Mcclain, Treatment of alcoholic liver disease, Therapeutic Advances in Gastroenterology, vol.4, issue.1, pp.63-81, 2011.

H. Fujii, N. Et, and . Kawada, « Inflammation and Fibrogenesis in Steatohepatitis, Journal of Gastroenterology, vol.47, issue.3, pp.215-240, 2012.

,

E. Gäbele, K. Dostert, C. Hofmann, R. Wiest, J. Schölmerich et al., « DSS Induced Colitis Increases Portal LPS Levels and Enhances Hepatic Inflammation and Fibrogenesis in Experimental NASH, Journal of Hepatology, vol.55, issue.6, pp.1391-99, 2011.

D. Galaris and K. Pantopoulos, « Oxidative Stress and Iron Homeostasis: Mechanistic and Health Aspects, Critical Reviews in Clinical Laboratory Sciences, vol.45, issue.1, pp.1-23, 2008.

M. Garcia, R. Moreno, S. Guéant-rodriguez, P. Pooya, J. Brachet et al., « Methyl Donor Deficiency Induces Cardiomyopathy through Altered Methylation/Acetylation of PGC-1? by PRMT1 and SIRT1, The Journal of Pathology, vol.225, issue.3, pp.324-359, 2011.

G. T. Gerhard and P. B. Duell, Homocysteine and Atherosclerosis, vol.10, pp.417-445, 1999.

R. Ghemrawi, S. Pooya, S. Lorentz, G. Gauchotte, C. Arnold et al., « Decreased Vitamin B12 Availability Induces ER Stress through Impaired SIRT1-Deacetylation of HSF1, Cell Death & Disease, vol.4, 2013.

S. Ghoshal, J. Witta, and J. Zhong, « Chylomicrons Promote Intestinal Absorption of Lipopolysaccharides », Journal of Lipid Research, vol.50, issue.1, pp.90-97, 2009.

G. Goh, A. J. Boon-bee, and . Mccullough, « Natural History of Nonalcoholic Fatty Liver Disease, Digestive Diseases and Sciences, vol.61, issue.5, pp.1226-1259, 2016.

J. Guéant, R. Elakoum, O. Ziegler, D. Coelho, E. Feigerlova et al., « Nutritional Models of Foetal Programming and Nutrigenomic and Epigenomic Dysregulations of Fatty Acid Metabolism in the Liver and Heart, Pflugers Archiv: European Journal of Physiology, vol.466, issue.5, pp.833-50, 2014.

J. Guéant, R. Guéant-rodriguez, G. Anello, P. Bosco, L. Brunaud et al., « Genetic Determinants of Folate and Vitamin B12 Metabolism: A Common Pathway in Neural Tube Defect and Down Syndrome?, Clinical Chemistry and Laboratory Medicine, vol.41, issue.11, pp.1473-77, 2003.

J. Guéant, F. Namour, R. Guéant-rodriguez, and J. Daval, « Folate and Fetal Programming: A Play in Epigenomics?, Trends in Endocrinology and Metabolism: TEM, vol.24, issue.6, pp.279-89, 2013.

A. Guilherme, J. V. Virbasius, V. Puri, M. P. Et, and . Czech, , 2008.

, Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes », Nature reviews. Molecular cell biology, vol.9, issue.5, pp.367-77

J. Halfvarson, L. Bodin, C. Tysk, E. Lindberg, G. Et et al., « Inflammatory Bowel Disease in a Swedish Twin Cohort: A Long-Term Follow-up of Concordance and Clinical Characteristics, Gastroenterology, vol.124, issue.7, pp.385-393, 2003.

R. B. Hamanaka, S. Et-navdeep, and . Chandel, « Mitochondrial Reactive Oxygen Species Regulate Cellular Signaling and Dictate Biological Outcomes », Trends in Biochemical Sciences, vol.35, issue.9, pp.505-518, 2010.

A. L. Harte, F. Nancy, . Da, S. J. Silva, . Creely et al., « Elevated Endotoxin Levels in Non-Alcoholic Fatty Liver Disease ». Journal of Inflammation, vol.7, 2010.

,

K. Hassan and V. Bhalla, Mohammed Ezz El Regal, et H. Hesham A-Kader. 2014. « Nonalcoholic Fatty Liver Disease: A Comprehensive Review of a Growing Epidemic, World Journal of Gastroenterology, vol.20, issue.34, pp.12082-101

,

J. Henao-mejia, E. Elinav, C. Jin, L. Hao, W. Z. Mehal et al., Inflammasome-Mediated Dysbiosis Regulates Progression of NAFLD and Obesity, Nature, vol.482, issue.7384, pp.179-85, 2012.

,

L. Hersoug, P. Møller, and E. S. Loft, « Gut Microbiota-Derived Lipopolysaccharide Uptake and Trafficking to Adipose Tissue: Implications for Inflammation and Obesity, Obesity Reviews, vol.17, issue.4, pp.297-312, 2016.

M. J. Holness, P. W. Caton, and M. C. Sugden, Acute and long-term nutrient-led modifications of gene expression: potential role of SIRT1 as a central co-ordinator of short and longer-term programming of tissue function, Nutr. Burbank Los Angel. Cty. Calif, vol.26, pp.491-501, 2010.

J. Hugot, C. Alberti, D. Berrebi, E. Bingen, and J. Cézard, « Crohn's Disease: The Cold Chain Hypothesis, The Lancet, vol.362, issue.9400, pp.15024-15030, 2003.

R. Hultcrantz, N. Et, and . Gabrielsson, « Patients with Persistent Elevation of Aminotransferases: Investigation with Ultrasonography, Radionuclide Imaging and Liver Biopsy », Journal of Internal Medicine, vol.233, issue.1, pp.7-12, 1993.

R. Hultcrantz, H. Glaumann, G. Lindberg, and L. H. Nilsson, Liver Investigation in 149 Asymptomatic Patients with Moderately Elevated Activities of Serum Aminotransferases, vol.21, pp.109-122, 1986.

. Iyer, S. K. Ramya, and . Tomar, « Folate: A Functional Food Constituent, Journal of Food Science, vol.74, issue.9, pp.114-122, 2009.

R. Jaenisch and A. Bird, « Epigenetic Regulation of Gene Expression: How the Genome Integrates Intrinsic and Environmental Signals », Nature Genetics, vol.33, pp.245-54, 2003.

W. Jia and C. Rajani, « The Influence of Gut Microbial Metabolism on the Development and Progression of Non-Alcoholic Fatty Liver Disease, Advances in Experimental Medicine and Biology, vol.1061, pp.95-110, 2018.

E. H. Jeninga, K. Schoonjans, A. , and J. , Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility, Oncogene, vol.29, pp.4617-4624, 2010.

S. C. Jones, R. E. Banks, A. Haidar, A. J. Gearing, I. K. Hemingway et al., Adhesion Molecules in Inflammatory Bowel Disease, vol.36, pp.724-754, 1995.

C. Ju and F. Tacke, Hepatic Macrophages in Homeostasis and Liver Diseases: From Pathogenesis to Novel Therapeutic Strategies, vol.13, pp.316-343, 2016.

H. Kamata, S. Honda, S. Maeda, L. Chang, H. Hirata et al., « Reactive Oxygen Species Promote TNFalpha-Induced Death and Sustained JNK Activation by Inhibiting MAP Kinase Phosphatases, Cell, vol.120, issue.5, pp.649-61, 2005.

M. D. Kappelman, L. Sheryl, K. Rifas-shiman, D. Kleinman, A. Ollendorf et al., « The Prevalence and Geographic Distribution of Crohn's Disease and Ulcerative Colitis in the United States, Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, vol.5, issue.12, pp.1424-1453, 2007.

,

A. Kaser, M. B. Flak, M. F. Tomczak, and R. S. Blumberg, « The Unfolded Protein Response and Its Role in Intestinal Homeostasis and Inflammation, Experimental Cell Research, vol.317, pp.2772-79, 2011.

Y. Kawano and D. E. Cohen, « Mechanisms of Hepatic Triglyceride Accumulation in Non-Alcoholic Fatty Liver Disease, Journal of Gastroenterology, vol.48, issue.4, pp.434-475, 2013.

R. Kerek, A. Geoffroy, A. Bison, N. Martin, N. Akchiche et al., « Early Methyl Donor Deficiency May Induce Persistent Brain Defects by Reducing Stat3 Signaling Targeted by MiR-124, Cell Death & Disease, vol.4, p.755, 2013.

K. Kim, S. Friso, S. Et, and . Choi, « DNA Methylation, an Epigenetic Mechanism Connecting Folate to Healthy Embryonic Development and Aging, The Journal of Nutritional Biochemistry, vol.20, issue.12, pp.917-943, 2009.

,

D. E. Kleiner, M. Elizabeth, M. Brunt, C. Van-natta, M. J. Behling et al., « Design and Validation of a Histological Scoring System for Nonalcoholic Fatty Liver Disease, Hepatology, vol.41, issue.6, pp.1313-1334, 2005.

M. Kojima, K. Et, and . Kangawa, Ghrelin: Structure and Function, vol.85, pp.495-522, 2005.

. Krajmalnik-brown, Z. Rosa, D. Ilhan, E. Kang, K. John et al., « Effects of Gut Microbes on Nutrient Absorption and Energy Regulation ». Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, vol.27, pp.201-215, 2012.

M. Krawczyk, L. Bonfrate, and . Et-piero-portincasa, « Nonalcoholic Fatty Liver Disease ». Best Practice & Research. Clinical Gastroenterology, vol.24, issue.5, pp.695-708, 2010.

J. Kwon, S. Lee, K. Yang, Y. Ahn, Y. Kim et al., « Reversible Oxidation and Inactivation of the Tumor Suppressor PTEN in Cells Stimulated with Peptide Growth Factors, Proceedings of the National Academy of Sciences of the United States of America, vol.101, issue.47, pp.16419-16443, 2004.

K. Lapumnuaypol, N. Kanjanahattakij, D. Pisarcik, C. Thongprayoon, K. Wijarnpreecha et al., Effects of Inflammatory Bowel Disease Treatment on the Risk of Nonalcoholic Fatty Liver Disease: A Meta-Analysis, vol.30, pp.854-60, 2018.

J. K. Lau, X. Ching, . Zhang, J. Et, and . Yu, « Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances, The Journal of Pathology, vol.241, issue.1, pp.36-44, 2017.

F. Laugerette, C. Vors, A. Géloën, M. Chauvin, C. Soulage et al., Emulsified Lipids Increase Endotoxemia: Possible Role in Early Postprandial Low-Grade Inflammation, vol.22, pp.53-59, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00486697

S. Leoni, F. Tovoli, L. Napoli, I. Serio, S. Ferri et al.,

, « Current Guidelines for the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review with, Comparative Analysis ». World Journal of Gastroenterology, vol.24, issue.30, p.3361

S. Lesage, H. Zouali, J. Cézard, J. Colombel, J. Belaiche et al., « CARD15/NOD2 Mutational Analysis and Genotype-Phenotype Correlation in 612 Patients with Inflammatory Bowel Disease, American Journal of Human Genetics, vol.70, issue.4, pp.845-57, 2002.

R. E. Ley, F. Bäckhed, P. Turnbaugh, C. A. Lozupone, R. D. Knight et al., Proceedings of the National Academy of Sciences of the United States of America, vol.102, pp.11070-75, 2005.

R. E. Ley, J. Peter, S. Turnbaugh, . Klein, J. I. Et et al., Microbial Ecology: Human Gut Microbes Associated with Obesity, vol.444, pp.1022-1045, 2006.

J. Liu, Z. Zhuang, D. Bian, X. Ma, Y. Xun et al., « Toll-like Receptor-4 Signalling in the Progression of Non-Alcoholic Fatty Liver Disease Induced by High-Fat and High-Fructose Diet in Mice, Clinical and Experimental Pharmacology & Physiology, vol.41, issue.7, pp.482-88, 2014.

. Liu, R. D. Wensheng, T. Baker, L. Bhatia, . Zhu et al., Pathogenesis of Nonalcoholic Steatohepatitis, vol.73, pp.1969-87, 2016.

G. Marchesini, E. Bugianesi, G. Forlani, F. Cerrelli, M. Lenzi et al., Nonalcoholic Fatty Liver, Steatohepatitis, and the Metabolic Syndrome, vol.37, pp.917-940, 2003.

A. Marengo, R. Jouness, E. Et, and . Bugianesi, « Progression and Natural History of Nonalcoholic Fatty Liver Disease in Adults, Clinics in Liver Disease, Non-Alcoholic Fatty Liver Disease, vol.20, issue.2, pp.313-337, 2016.

,

R. Masalha, I. Rudoy, I. Volkov, N. Yusuf, I. Wirguin et al., Symptomatic Dietary Vitamin B12 Deficiency in a Nonvegetarian Population, vol.112, pp.413-429, 2002.

, , pp.1031-1039

M. Masouminia, S. Samadzadeh, A. S. Mendoza, B. A. French, B. Tillman et al.,

, « Upregulation of Autophagy Components in Alcoholic Hepatitis and Nonalcoholic Steatohepatitis, vol.101, pp.81-88

S. C. Matherly, P. Et, and . Puri, Mechanisms of Simple Hepatic Steatosis: Not so Simple after All, vol.16, pp.505-529, 2012.

,

N. Matsushita, T. Osaka, I. Haruta, H. Ueshiba, N. Yanagisawa et al.,

. Hashimoto, « Effect of Lipopolysaccharide on the Progression of Non-Alcoholic Fatty Liver Disease in High Caloric Diet-Fed Mice, Scandinavian Journal of Immunology, vol.83, issue.2, pp.109-127, 2016.

C. J. Mcclain, L. Sri-prakash, S. S. Mokshagundam, Z. Barve, D. B. Song et al., et Ion Deaciuc. 2004. « Mechanisms of Non-Alcoholic Steatohepatitis, vol.34, pp.67-79

,

C. E. Mcgowan, P. Jones, M. D. Long, and S. A. Barritt, Changing Shape of Disease: Nonalcoholic Fatty Liver Disease in Crohn?s Disease-A Case Series and Review of the Literature »: Inflammatory Bowel Diseases, vol.18, pp.49-54, 2012.

E. Mclean, B. De-benoist, and L. H. Allen, « Review of the Magnitude of Folate and Vitamin B12 Deficiencies Worldwide, Food and Nutrition Bulletin, vol.29, issue.2, pp.38-51, 2008.

S. Melgar, A. Karlsson, E. Et, and . Michaëlsson, « Acute Colitis Induced by Dextran Sulfate Sodium Progresses to Chronicity in C57BL/6 but Not in BALB/c Mice: Correlation between Symptoms and Inflammation, American Journal of Physiology. Gastrointestinal and Liver Physiology, vol.288, issue.6, pp.1328-1338, 2005.

,

H. Melhem, F. Hansmannel, A. Bressenot, S. Battaglia-hsu, V. Billioud et al., MethylDeficient Diet Promotes Colitis and SIRT1-Mediated Endoplasmic Reticulum Stress, vol.65, pp.595-606, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01682756

L. Miele, V. Valenza, G. L. Torre, M. Montalto, G. Cammarota et al., « Increased Intestinal Permeability and Tight Junction Alterations in Nonalcoholic Fatty Liver Disease, Hepatology, vol.49, issue.6, pp.1877-87, 2009.

H. Min, A. Kapoor, M. Fuchs, F. Mirshahi, H. Zhou et al., 2012. « Increased Hepatic Synthesis and Dysregulation of Cholesterol Metabolism Is Associated with the Severity of Nonalcoholic Fatty Liver Disease, Cell Metabolism, vol.15, issue.5, pp.665-74

K. Miura, « Role of Gut Microbiota and Toll-like Receptors in Nonalcoholic Fatty Liver Disease, World Journal of Gastroenterology, vol.20, issue.23, p.7381, 2014.

K. Miura, Y. Kodama, S. Inokuchi, B. Schnabl, T. Aoyama et al., « Toll-like Receptor 9 Promotes Steatohepatitis by Induction of Interleukin-1beta in Mice, Gastroenterology, vol.139, issue.1, pp.323-334, 2010.

K. Miura, L. Yang, N. Van-rooijen, H. Ohnishi, E. Et et al., , 2012.

, Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2, American Journal of Physiology -Gastrointestinal and Liver Physiology, vol.302, issue.11, pp.1310-1331

A. R. Moschen, S. Kaser, H. Et, and . Tilg, « Non-Alcoholic Steatohepatitis: A Microbiota-Driven Disease, Trends in Endocrinology and Metabolism: TEM, vol.24, issue.11, pp.537-582, 2013.

. Mouzaki, E. M. Marialena, B. M. Comelli, J. Arendt, S. K. Bonengel et al., Intestinal Microbiota in Patients with Nonalcoholic Fatty Liver Disease ». Hepatology, vol.58, pp.120-147, 2013.

P. Mulder, A. M. Van-den-hoek, and R. Kleemann, « The CCR2 Inhibitor Propagermanium Attenuates Diet-Induced Insulin Resistance, Adipose Tissue Inflammation and Non-Alcoholic Steatohepatitis », PloS One, vol.12, issue.1, p.169740, 2017.

J. A. Murray, « The Widening Spectrum of Celiac Disease, The American Journal of Clinical Nutrition, vol.69, issue.3, pp.354-65, 1999.

S. N. Murthy, H. S. Cooper, H. Shim, R. S. Shah, S. A. Ibrahim et al., Treatment of Dextran Sulfate Sodium-Induced Murine Colitis by Intracolonic Cyclosporin ». Digestive Diseases and Sciences, vol.38, pp.1722-1756, 1993.

G. Musso, R. Gambino, and M. Cassader, « Non-Alcoholic Fatty Liver Disease from Pathogenesis to Management: An Update, Obesity Reviews: An Official Journal of the International Association for the Study of Obesity, vol.11, issue.6, pp.430-475, 2010.

,

K. Nakatani, S. Seki, N. Kawada, T. Kitada, T. Yamada et al., « Expression of SPARC by Activated Hepatic Stellate Cells and Its Correlation with the Stages of Fibrogenesis in Human Chronic Hepatitis, Virchows Archiv: An International Journal of Pathology, vol.441, issue.5, pp.466-74, 2002.

. Naser, A. Saleh, M. Arce, A. Khaja, M. Fernandez et al., Sammer Elwasila, et Saisathya Thanigachalam. 2012. « Role of ATG16L, NOD2 and IL23R in Crohn's Disease Pathogenesis, World Journal of Gastroenterology, vol.18, issue.5, pp.412-436

. Neuschwander-tetri, A. Brent, H. Et-stephen, and . Caldwell, Nonalcoholic Steatohepatitis: Summary of an AASLD Single Topic Conference, vol.37, pp.1202-1221, 2003.

G. C. Nguyen, A. Tuskey, T. Dassopoulos, M. L. Harris, and S. R. Brant, « Rising Hospitalization Rates for Inflammatory Bowel Disease in the United States between, Inflammatory Bowel Diseases, vol.13, issue.12, pp.1529-1564, 1998.

J. Pais-de-barros, T. Gautier, W. Sali, C. Adrie, H. Choubley et al., « Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay, Journal of Lipid Research, vol.56, issue.7, pp.1363-69, 2015.

S. V. Pawar, G. Vinay, A. S. Zanwar, . Choksey, . Ashok-r-mohite et al.,

, « Most Overweight and Obese Indian Children Have Nonalcoholic Fatty Liver Disease, Ann Hepatol, vol.15, issue.9, pp.853-861

G. Paz-filho, C. Mastronardi, T. Delibasi, M. Wong, J. Et et al.,

, Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy, Arquivos brasileiros de endocrinologia e metabologia, vol.54, issue.8, pp.690-97

A. D. Peña, I. Leclercq, J. Field, J. George, B. Jones et al., « NF-?B Activation, Rather Than TNF, Mediates Hepatic Inflammation in a Murine Dietary Model of Steatohepatitis, Gastroenterology, vol.129, issue.5, pp.1663-74, 2005.

. Pendyala, J. M. Swaroop, . Walker, R. Peter, and . Holt, « A High-Fat Diet Is Associated With Endotoxemia That Originates From the Gut, Gastroenterology, vol.142, issue.5, pp.1100-1101, 2012.

. Peyrin-biroulet, A. Laurent, W. J. Cieza, M. Sandborn, Y. Coenen et al., Jean-Frédéric Colombel, et International Programme to Develop New Indexes for Crohn's Disease (IPNIC) group. 2012. « Development of the First Disability Index for Inflammatory Bowel Disease Based on the International Classification of Functioning, Disability and Health, Gut, vol.61, issue.2, pp.241-288

,

. Peyrin-biroulet, R. Laurent, M. Rodriguez-guéant, P. Chamaillard, B. Desreumaux et al.,

, « Vascular and Cellular Stress in Inflammatory Bowel Disease: Revisiting the Role of Homocysteine, vol.102, pp.1108-1123

C. Pirola, T. F. Jose, A. L. Gianotti, M. Burgueño, C. F. Rey-funes et al., « Epigenetic Modification of Liver Mitochondrial DNA Is Associated with Histological Severity of Nonalcoholic Fatty Liver Disease, Gut, vol.62, issue.9, pp.1356-63, 2013.

R. Poddar, N. Sivasubramanian, P. M. Dibello, K. Robinson, and D. W. Jacobsen, « Homocysteine Induces Expression and Secretion of Monocyte Chemoattractant Protein-1 and Interleukin-8 in Human Aortic Endothelial Cells: Implications for Vascular Disease, Circulation, vol.103, issue.22, pp.2717-2740, 2001.

I. P. Pogribny, P. Volodymyr, T. V. Tryndyak, S. Bagnyukova, B. Melnyk et al.,

E. «-hepatic, Phenotype Predetermines Individual Susceptibility to Hepatic Steatosis in Mice Fed a Lipogenic Methyl-Deficient Diet, Journal of Hepatology, vol.51, issue.1, pp.176-86

S. Pooya, S. Blaise, M. M. Garcia, J. Giudicelli, J. Alberto et al., « Methyl Donor Deficiency Impairs Fatty Acid Oxidation through PGC-1? Hypomethylation and Decreased ER-?, ERR-?, and HNF-4? in the Rat Liver, Journal of Hepatology, vol.57, issue.2, pp.344-51, 2012.

M. Principi, A. Iannone, G. Losurdo, M. Mangia, E. Shahini et al., Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors, vol.24, pp.1589-96, 2018.

A. Propst, T. Propst, G. Judmaier, and W. Vogel, Prognosis in Nonalcoholic Steatohepatitis, vol.108, p.1607, 1995.

N. M. Put, H. J. Van-der, and . Blom, « Neural Tube Defects and a Disturbed Folate Dependent Homocysteine Metabolism, European Journal of Obstetrics, Gynecology, and Reproductive Biology, vol.92, issue.1, pp.57-61, 2000.

S. B. Rafnsson, P. Saravanan, R. S. Bhopal, S. Et-chittaranjan, and . Yajnik, « Is a Low Blood Level of Vitamin B12 a Cardiovascular and Diabetes Risk Factor? A Systematic Review of Cohort Studies, European Journal of Nutrition, vol.50, issue.2, pp.97-106, 2011.

U. Ramakrishnan, « Prevalence of Micronutrient Malnutrition Worldwide, Nutrition Reviews, vol.60, issue.5, pp.46-52, 2002.

M. Raman, I. Ahmed, P. M. Gillevet, C. S. Probert, N. M. Ratcliffe et al., « Fecal Microbiome and Volatile Organic Compound Metabolome in Obese Humans With Nonalcoholic Fatty Liver Disease, Clinical Gastroenterology and Hepatology, vol.11, issue.7, pp.868-875, 2013.

F. Ratter, C. Gassner, V. Shatrov, and V. Lehmann, « Modulation of Tumor Necrosis Factor-Alpha-Mediated Cytotoxicity by Changes of the Cellular Methylation State: Mechanism and in Vivo Relevance, International Immunology, vol.11, issue.4, pp.519-546, 1999.

H. A. Ravin, D. Rowley, C. Jenkins, and E. J. Fine, « On the Absorption of Bacterial Endotoxin from the Gastro-Intestinal Tract of the Normal and Shocked Animal, Journal of Experimental Medicine, vol.112, issue.5, pp.783-92, 1960.

A. Rebollo, N. Roglans, M. Baena, R. M. Sánchez, M. Merlos et al., « Liquid Fructose Downregulates Sirt1 Expression and Activity and Impairs the Oxidation of Fatty Acids in Rat and Human Liver Cells, Biochimica Et Biophysica Acta, vol.1841, issue.4, pp.514-538, 2014.

,

R. Rector, A. Scott, and . Ibdah, « Fatty Acid Oxidation Disorders: Maternal Health and Neonatal Outcomes, Seminars in Fetal & Neonatal Medicine, vol.15, issue.3, pp.122-150, 2010.

C. A. Rivera, P. Adegboyega, N. Van-rooijen, A. Tagalicud, M. Allman et al., « Toll-like Receptor-4 Signaling and Kupffer Cells Play Pivotal Roles in the Pathogenesis of Non-Alcoholic Steatohepatitis, Journal of Hepatology, vol.47, issue.4, pp.571-79, 2007.

K. Cusi, Role of Insulin Resistance and Lipotoxicity in Non-Alcoholic Steatohepatitis, Clinics in Liver Disease, vol.13, issue.4, pp.545-63, 2009.

,

S. Romeo, J. Kozlitina, C. Xing, A. Pertsemlidis, D. Cox et al., « Genetic Variation in PNPLA3 Confers Susceptibility to Nonalcoholic Fatty Liver Disease », Nature Genetics, vol.40, issue.12, pp.1461-65, 2008.

I. H. Rosenberg, Effects of Folate and Vitamin B12 on Cognitive Function in Adults and the Elderly, vol.29, pp.132-142, 2008.

P. Rosenstiel, M. Fantini, K. Bräutigam, T. Kühbacher, G. H. Waetzig et al., « TNF-Alpha and IFN-Gamma Regulate the Expression of the NOD2 (CARD15) Gene in Human Intestinal Epithelial Cells, Gastroenterology, vol.124, issue.4, pp.1001-1010, 2003.

M. G. Russel, A. Volovics, E. J. Schoon, H. J. Erik, R. F. Van-wijlick et al., « Inflammatory Bowel Disease: Is There Any Relation between Smoking Status and Disease Presentation?, Inflammatory Bowel Diseases, vol.4, issue.3, pp.182-86, 1998.

A. J. Sanyal, C. Campbell-sargent, F. Mirshahi, W. B. Rizzo, M. J. Contos et al., Nonalcoholic Steatohepatitis: Association of Insulin Resistance and Mitochondrial Abnormalities, vol.120, pp.1183-92, 2001.

S. Palumbo, S. Chiara, C. Restellini, A. Chao, C. Aruljothy et al., « Screening for Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Diseases: A Cohort Study Using Transient Elastography ». Inflammatory Bowel Diseases, 2018.

S. Schuster, D. Cabrera, M. Arrese, A. E. Et, and . Feldstein, « Triggering and Resolution of Inflammation in NASH », Nature Reviews Gastroenterology & Hepatology, vol.15, issue.6, pp.349-64, 2018.

J. M. Scott, « Evidence of Folic Acid and Folate in the Prevention of Neural Tube Defects, Bibliotheca Nutritio Et Dieta, vol.55, pp.192-95, 2001.

E. Seki, S. D. Minicis, C. H. Osterreicher, J. Kluwe, Y. Osawa et al., « TLR4 Enhances TGF-Beta Signaling and Hepatic Fibrosis », Nature Medicine, vol.13, issue.11, pp.1324-1356, 2007.

M. Shimada, E. Hashimoto, M. Taniai, K. Hasegawa, H. Okuda et al., « Hepatocellular Carcinoma in Patients with Non-Alcoholic Steatohepatitis, Journal of Hepatology, vol.37, issue.1, pp.154-60, 2002.

B. L. Shneider, R. González-peralta, E. A. Et, and . Roberts, Controversies in the Management of Pediatric Liver Disease: Hepatitis B, C and NAFLD: Summary of a Single Topic Conference ». Hepatology, vol.44, pp.1344-54, 2006.

R. Singh, S. Kaushik, Y. Wang, Y. Xiang, I. Novak et al., Autophagy Regulates Lipid Metabolism, vol.458, pp.1131-1166, 2009.

R. Singh, Y. Xiang, Y. Wang, K. Baikati, A. M. Cuervo et al., Autophagy Regulates Adipose Mass and Differentiation in Mice, vol.119, pp.3329-3368, 2009.

U. P. Singh, P. Narendra, E. A. Singh, R. L. Murphy, R. Price et al., Chemokine and cytokine levels in inflammatory bowel disease patients, vol.77, pp.44-49, 2016.

,

U. P. Singh, P. Narendra, B. Singh, L. J. Singh, R. L. Hofseth et al., « Resveratrol (Trans-3,5,4'-Trihydroxystilbene) Induces Silent Mating Type Information Regulation-1 and down-Regulates Nuclear Transcription Factor-KappaB Activation to Abrogate Dextran Sulfate Sodium-Induced Colitis, The Journal of Pharmacology and Experimental Therapeutics, vol.332, issue.3, pp.829-868, 2010.

S. Skugor, A. Skugor, M. Todorcevi?, J. Torgersen, B. Ruyter et al., « Exposure to Lipopolysaccharide Induces Immune Genes in Cultured Preadipocytes of Atlantic Salmon, Fish & Shellfish Immunology, vol.29, issue.5, pp.817-841, 2010.

A. Smith, Y. David, H. Kim, and . Refsum, « Is Folic Acid Good for Everyone?, The American Journal of Clinical Nutrition, vol.87, issue.3, pp.517-550, 2008.

C. Söderberg, P. Stål, J. Askling, H. Glaumann, G. Lindberg et al., « Decreased Survival of Subjects with Elevated Liver Function Tests during a 28-year Follow-up, Hepatology, vol.51, issue.2, pp.595-602, 2010.

,

A. Sonnenberg and J. Chang, « Time Trends of Physician Visits for Crohn's Disease and Ulcerative Colitis in the United States, Inflammatory Bowel Diseases, vol.14, issue.2, pp.249-52, 1960.

A. Sourianarayanane, G. Garg, T. H. Smith, M. I. Butt, and J. Arthur,

B. Mccullough and . Shen, « Risk Factors of Non-Alcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Disease, Journal of Crohn's & Colitis, vol.7, issue.8, pp.279-285, 2013.

L. Spahr, F. Negro, G. Leandro, O. Marinescu, K. J. Goodman et al., « Impaired Hepatic Mitochondrial Oxidation Using the 13C-Methionine Breath Test in Patients with Macrovesicular Steatosis and Patients with Cirrhosis », Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, vol.9, issue.1, pp.6-11, 2003.

E. K. Speliotes, M. Laura, J. Yerges-armstrong, R. Wu, and . Hernaez,

C. D. Kim, V. Palmer, and . Gudnason, « Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits, PLoS Genetics, vol.7, issue.3, 2011.

M. D. Spencer, J. Timothy, R. W. Hamp, L. M. Reid, S. H. Fischer et al., « Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency, Gastroenterology, vol.140, issue.3, pp.976-86, 2011.

C. P. Stewart, K. J. Christian, M. Schulze, S. C. Arguello, . Leclerq et al., « Low Maternal Vitamin B-12 Status Is Associated with Offspring Insulin Resistance Regardless of Antenatal Micronutrient Supplementation in Rural Nepal, The Journal of Nutrition, vol.141, issue.10, pp.1912-1929, 2011.

P. J. Stover, « Polymorphisms in 1-Carbon Metabolism, Epigenetics and FolateRelated Pathologies, Journal of Nutrigenetics and Nutrigenomics, vol.4, issue.5, pp.293-305, 2011.

G. Szabo, A. Velayudham, L. Romics, P. Et, and . Mandrekar, « Modulation of Non-Alcoholic Steatohepatitis by Pattern Recognition Receptors in Mice: The Role of Toll-like Receptors 2 and 4, Clinical and Experimental Research, vol.29, issue.11, pp.140-145, 2005.

S. M. Tanner, Z. Li, R. Bisson, C. Acar, C. Oner et al., Genetically Heterogeneous Selective Intestinal Malabsorption of Vitamin B12: Founder Effects, Consanguinity, and High Clinical Awareness Explain Aggregations in Scandinavia and the Middle East, vol.23, pp.327-360, 2004.

C. Teyssier, H. Ma, R. Emter, A. Kralli, and M. R. Stallcup, Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation, Genes Dev, vol.19, pp.1466-1473, 2005.

N. Than, . Ni, P. N. Et, and . Newsome, « A Concise Review of Non-Alcoholic Fatty Liver Disease, Atherosclerosis, vol.239, issue.1, pp.192-202, 2015.

,

W. L. Thompson, L. J. Et, and . Van-eldik, « Inflammatory Cytokines Stimulate the Chemokines CCL2/MCP-1 and CCL7/MCP-3 through NFkB and MAPK Dependent Pathways in Rat Astrocytes, Brain Research, vol.1287, pp.47-57, 2009.

S. Thuy, R. Ladurner, V. Volynets, S. Wagner, S. Strahl et al., Nonalcoholic Fatty Liver Disease in Humans Is Associated with Increased Plasma Endotoxin and Plasminogen Activator Inhibitor 1 Concentrations and with Fructose Intake, vol.138, pp.1452-55, 2008.

H. Tilg and A. M. Diehl, Cytokines in Alcoholic and Nonalcoholic Steatohepatitis, vol.343, pp.1467-76, 2000.

V. Trak-smayra, V. Paradis, J. Massart, S. Nasser, V. Jebara et al., Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or highcalorie diet, Int. J. Exp. Pathol, vol.92, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00741688

V. Tremaroli and F. Bäckhed, « Functional Interactions between the Gut Microbiota and Host Metabolism », Nature, vol.489, issue.7415, pp.242-291, 2012.

,

P. J. Turnbaugh, K. Vanessa, J. J. Ridaura, F. E. Faith, R. Rey et al., The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice, vol.1, pp.6-14, 2009.

. Ueland, M. Per, H. Refsum, A. A. Shirley, . Beresford et al., « The Controversy over Homocysteine and Cardiovascular Risk, The American Journal of Clinical Nutrition, vol.72, issue.2, pp.324-356, 2000.

A. Velayudham, A. Dolganiuc, M. Ellis, J. Petrasek, K. Kodys et al., « VSL#3 Probiotic Treatment Attenuates Fibrosis without Changes in Steatohepatitis in a Diet-Induced Nonalcoholic Steatohepatitis Model in Mice, Hepatology, vol.49, issue.3, pp.989-97, 2009.

,

U. Vespasiani-gentilucci, S. Carotti, A. Onetti-muda, G. Perrone, S. Ginanni-corradini et al., « Toll-like Receptor-4 Expression by Hepatic Progenitor Cells and Biliary Epithelial Cells in HCV-Related Chronic Liver Disease, Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, vol.25, issue.4, pp.576-89, 2012.

U. Vespasiani-gentilucci, S. Carotti, G. Perrone, C. Mazzarelli, G. Galati et al., « Hepatic Toll-like Receptor 4 Expression Is Associated with Portal Inflammation and Fibrosis in Patients with NAFLD, Liver International: Official Journal of the International Association for the Study of the Liver, vol.35, issue.2, pp.569-81, 2015.

P. Viatour, M. Merville, V. Bours, A. Et, and . Chariot, « Phosphorylation of NF-?B and I?B Proteins: Implications in Cancer and Inflammation », Trends in Biochemical Sciences, vol.30, issue.1, pp.43-52, 2005.

L. A. Videla, G. Tapia, R. Rodrigo, P. Pettinelli, D. Haim et al., « Liver NF-KappaB and AP-1 DNA Binding in Obese Patients, Obesity (Silver Spring, Md.), vol.17, issue.5, pp.973-79, 2009.

,

. Volynets, M. A. Valentina, S. Küper, I. B. Strahl, A. Maier et al., « Nutrition, Intestinal Permeability, and Blood Ethanol Levels Are Altered in Patients with Nonalcoholic Fatty Liver Disease (NAFLD), Digestive Diseases and Sciences, vol.57, issue.7, pp.1932-1973, 2012.

A. C. Vreugdenhil, H. Corine, T. Rousseau, J. Hartung, M. Willem et al., Cornelis van 't Veer, et Wim A. Buurman. 2003. « Lipopolysaccharide (LPS)-Binding Protein Mediates LPS Detoxification by Chylomicrons, vol.170, pp.1399-1405

J. Wehkamp, M. Schmid, K. Fellermann, E. F. Et, and . Stange, « Defensin Deficiency, Intestinal Microbes, and the Clinical Phenotypes of Crohn's Disease », Journal of Leukocyte Biology, vol.77, issue.4, pp.460-65, 2005.

. Wang, C. W. Guoping, F. L. Woo, Y. L. Sung, . Siow et al., « Increased Monocyte Adhesion to Aortic Endothelium in Rats with Hyperhomocysteinemia: Role of Chemokine and Adhesion Molecules, Arteriosclerosis, Thrombosis, and Vascular Biology, vol.22, issue.11, pp.1777-83, 2002.

X. Wang, X. Zhang, S. H. Eagle, X. Chu, W. Chen et al., « Defective Lysosomal Clearance of Autophagosomes and Its Clinical Implications in Nonalcoholic Steatohepatitis, FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, vol.32, issue.1, pp.37-51, 2018.

M. G. Ward, C. Viraj, . Kariyawasam, B. Sathis, . Mogan et al., « Prevalence and Risk Factors for Functional Vitamin B12 Deficiency in Patients with Crohn's Disease », Inflammatory Bowel Diseases, vol.21, issue.12, pp.2839-2886, 2015.

D. Watkins and D. S. Rosenblatt, Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity, Am. J. Med. Genet, vol.34, pp.427-434, 1989.

D. Watkins and D. S. Rosenblatt, Inborn errors of cobalamin absorption and metabolism, Am. J. Med. Genet. C Semin. Med. Genet, vol.157, pp.33-44, 2011.

J. Weingärtner, K. Lotz, J. Fanghänel, T. Gedrange, V. Bienengräber et al., « Induction and Prevention of Cleft Lip, Alveolus and Palate and Neural Tube Defects with Special Consideration of B Vitamins and the Methylation Cycle », Journal of Orofacial Orthopedics = Fortschritte Der Kieferorthopadie: Organ/Official Journal Deutsche Gesellschaft Fur Kieferorthopadie, vol.68, issue.4, pp.266-77, 2007.

A. Wigg, R. Roberts-thomson, P. Dymock, R. Mccarthy, . Grose et al., « The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor ? in the pathogenesis of non-alcoholic steatohepatitis, Gut, vol.48, issue.2, pp.206-217, 2001.

K. H. Williams, N. A. Shackel, M. D. Gorrell, S. V. Mclennan, and S. M. Twigg, Diabetes and Nonalcoholic Fatty Liver Disease: A Pathogenic Duo, vol.34, pp.84-129, 2013.

, « Molecular Characterization of the Fecal Microbiota in Patients with Nonalcoholic Steatohepatitis -A Longitudinal Study, PLoS ONE, vol.8, issue.4

,

C. S. Yajnik, S. S. Deshpande, A. A. Jackson, H. Refsum, S. Rao et al., « Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study, Diabetologia, vol.51, issue.1, pp.29-38, 2008.

C. Yajnik, . Sakerlal, . Et-urmila-shailesh, and . Deshmukh, « Fetal Programming: Maternal Nutrition and Role of One-Carbon Metabolism, Endocrine and Metabolic Disorders, vol.13, pp.121-148, 2012.

Z. Yang, H. Miyahara, J. Takeo, M. Et, and . Katayama, « Diet High in Fat and Sucrose Induces Rapid Onset of Obesity-Related Metabolic Syndrome Partly through Rapid Response of Genes Involved in Lipogenesis, Insulin Signalling and Inflammation in Mice, Diabetology & Metabolic Syndrome, vol.4, issue.1, p.32, 2012.

T. Yoshimura, N. Yuhki, S. K. Moore, E. Appella, M. I. Lerman et al., « Human Monocyte Chemoattractant Protein-1 (MCP-1). Full-Length CDNA Cloning, Expression in Mitogen-Stimulated Blood Mononuclear Leukocytes, and Sequence Similarity to Mouse Competence Gene JE, FEBS Letters, vol.244, issue.2, pp.487-93, 1989.

. Younossi, Q. M. Zobair, M. Anstee, T. Marietti, L. Hardy et al., Global Burden of NAFLD and NASH: Trends, Predictions, Risk Factors and Prevention, 2018.

, Gastroenterology & Hepatology, vol.15, issue.1, pp.11-20

Z. M. Younossi, B. Aaron, D. Koenig, Y. Abdelatif, L. Fazel et al., « Global Epidemiology of Nonalcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes, Hepatology, vol.64, issue.1, pp.73-84, 2016.

Z. M. Younossi, L. Munkhzul-otgonsuren, C. Henry, A. Venkatesan, M. Mishra et al., Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Hepatocellular Carcinoma (HCC) in the United States from, 2004.

, Hepatology, vol.62, issue.6

K. L. Zambell, D. Mark, S. E. Fitch, and . Fleming, « Acetate and Butyrate Are the Major Substrates for de Novo Lipogenesis in Rat Colonic Epithelial Cells, The Journal of Nutrition, vol.133, issue.11, pp.3509-3524, 2003.

. Zeybel, D. A. Müjdat, . Mann, J. Et, and . Mann, Epigenetic Modifications as New Targets for Liver Disease Therapies, vol.59, pp.1349-53, 2013.

. Zhang, G. Xu-mei, Z. Huang, . Tian, J. X. Da-lin-ren et al., « Folate Stimulates ERK1/2 Phosphorylation and Cell Proliferation in Fetal Neural Stem Cells », Nutritional Neuroscience, vol.12, issue.5, pp.226-258, 2009.

,

, ) pendant 10 min, suivie de streptavidine-peroxydase (Kit Abcam Kit IHC de détection de HRP/DAB (ABC) spécifique de lapin (réf: ab64261 Abcam, Cambridge, Royaume-Uni) pendant 10 min. Les sections ont ensuite été incubées avec AEC (Leica Biosystems Ltd, Apre?s de?paraffinisation des coupes (4 µM d'e?paisseur), elles ont e?te?pre?traite?ese?te?pre?traite?es dans un tampon citrate, vol.1, p.400

, Notre hypothèse de base est que le régime MDD, le régime HE, les LPS du microbiote et l'inflammation intestinale (modèle Dextran Sodium Sulfate (DSS) comme déclencheurs et l'immunité innée en tant que modulateur font partie d'un même sce?nario conduisant à la NASH. Des rats carencés (MDD), soumis ou non au régime riche en graisse à l'âge adulte (HE) et expose?s ou non à deux inducteurs de l'inflammation locale et syste?mique, le DSS (inflammation intestinale) et les LPS (effets syste?miques de l'inflammation intestinale) ont été étudiés. Nous n'observons pas d'alte?ration de l'immuniteínne?e (TLR4) dans les groupes MDD/DSS, MDD/HE et MDD/HE/LPS. L'inflammation observe?e au niveau intestinal chez les rats MDD/DSS est également observée au niveau hépatique, avec de stéatose et activation de l'inflammasome et de la chimiokine MCP-1 et IL-1beta. De façon surprenante, cet effet systémique ne met pas en jeu la voie TLR4 et son ligand LPS même quand les rats étaitent exposés au LPS, pendant la gestation et la lactation produit une stéato-hépatite non alcoolique (NASH) chez les animaux soumis au re?gime riche en graisses (HE) pendant l'âge adulte, en de?pit d'une normalisation histologique et métabolique par un régime normal entre le sevrage (J21) et l'âge de puberté (J50)

/. Il-1?, mais pas par l'activation de TLR4 par translocation de LPS. L'immuniteínne?e n' étant pas impliquée même par l'injection directe du LPS, les effets respectifs et synergiques de régime MDD

, Our basic assumption is that MDD, HE diet, microbiota LPS and intestinal inflammation (Dextran Sodium Sulfate (DSS) model) as triggers and innate immunity as a modulator are part of the same scenario leading to NASH. Deficient rats (MDD), whether or not exposed to the high-fat diet in adulthood (HE) and whether or not exposed to two inducers of local and systemic inflammation, DSS (intestinal inflammation) or LPS (systemic effects intestinal inflammation) were studied. We did not observe alterations in innate immunity (TLR4) in the MDD/DSS, MDD/HE and MDD/HE/LPS groups. Inflammation observed in the intestines in MDD/DSS rats is also observed in the liver, with steatosis and activation of the inflammasome and chemokine MCP-1 and IL-1beta. Surprisingly, this systemic effect does not involve the TLR4 pathway and its ligand LPS even when the rats were exposed to LPS directly at the peritoneal level. Our study conclude that NASH favored by the systemic effects of Intestinal inflammation is mediated by MCP-1/IL-1?, but not by activation of TLR4 by translocation of LPS, Mots clés: Foie, maladie intestinale inflammatoire, récepteur Toll-like 4, Lipopolysaccarides, inflammation. Summary: Deficiency of methyl donors (folic acid and vitamin B12) (MDD) during pregnancy and lactation produces non-alcoholic steatohepatitis (NASH) in animals fed high fat (HE) diet, despite histological and metabolic normalization by a normal diet between weaning (J21) and puberty (J50)