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Role of Lipogenesis and Lipid Desaturases in Non-alcoholic Fatty Liver Disease

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Hepatic De Novo Lipogenesis and Regulation of Metabolism

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathological change characterized by the accumulation of triacylglycerol (TG) in hepatic lipid droplets (LD). NAFLD can range from a simple steatosis to Non-alcoholic steatohepatitis (NASH) characterized by hepatic injury, inflammation, and eventually fibrosis. NAFLD can also be associated with insulin resistance (IR), ER stress, oxidative stress and inflammation. The cause of NAFLD is due to modification of various metabolic pathways including increased fatty acid (FA) uptake and/or reduced FA oxidation, decreased VLDL secretion and increased de novo lipogenesis (DNL). NAFLD is often observed in obese patients where energy is in excess and energy expenditure is low. In these conditions, most of carbohydrates are converted into TG through DNL. We aim here to present the most recent studies demonstrating the key role of DNL in NAFLD development. A special focus will be made on desaturases especially the stearoyl CoA desaturase 1, a central enzyme implicated in fatty liver disease as well as on the delta 5 and delta 6 desaturases, two enzymes involved in the synthesis of omega 3 and omega 6 fatty acids.

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References

  • Abu-Elheiga L, Oh W, Kordari P, Wakil SJ (2003) Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc Natl Acad Sci U S A 100:10207–10212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahn SB, Jang K, Jun DW, Lee BH, Shin KJ (2014) Expression of liver X receptor correlates with intrahepatic inflammation and fibrosis in patients with nonalcoholic fatty liver disease. Dig Dis Sci 59:2975–2982

    Article  CAS  PubMed  Google Scholar 

  • Ameer F, Scandiuzzi L, Hasnain S, Kalbacher H, Zaidi N (2014) De novo lipogenesis in health and disease. Metabolism 63:895–902

    Article  CAS  PubMed  Google Scholar 

  • Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346:1221–1231

    Article  CAS  PubMed  Google Scholar 

  • Araya J, Rodrigo R, Videla LA, Thielemann L, Orellana M, Pettinelli P, Poniachik J (2004) 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. Clin Sci (Lond) 106:635–643

    Article  CAS  Google Scholar 

  • Araya J, Rodrigo R, Pettinelli P, Araya AV, Poniachik J, Videla LA (2010) Decreased liver fatty acid delta-6 and delta-5 desaturase activity in obese patients. Obesity (Silver Spring) 18:1460–1463

    Article  CAS  Google Scholar 

  • Beller M, Bulankina AV, Hsiao HH, Urlaub H, Jackle H, Kuhnlein RP (2010) PERILIPIN-dependent control of lipid droplet structure and fat storage in Drosophila. Cell Metab 12:521–532

    Article  CAS  PubMed  Google Scholar 

  • Benhamed F, Denechaud PD, Lemoine M, Robichon C, Moldes M, Bertrand-Michel J, Ratziu V, Serfaty L, Housset C, Capeau J, Girard J, Guillou H, Postic C (2012) The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans. J Clin Invest 122:2176–2194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berlanga A, Guiu-Jurado E, Porras JA, Auguet T (2014) Molecular pathways in non-alcoholic fatty liver disease. Clin Exp Gastroenterol 7:221–239

    PubMed  PubMed Central  Google Scholar 

  • Bitter A, Nussler AK, Thasler WE, Klein K, Zanger UM, Schwab M, Burk O (2015) Human sterol regulatory element-binding protein 1a contributes significantly to hepatic lipogenic gene expression. Cell Physiol Biochem 35:803–815

    Article  PubMed  Google Scholar 

  • Boden G, Song W, Duan X, Cheung P, Kresge K, Barrero C, Merali S (2011) Infusion of glucose and lipids at physiological rates causes acute endoplasmic reticulum stress in rat liver. Obesity (Silver Spring) 19:1366–1373

    Article  CAS  Google Scholar 

  • Brasaemle DL, Wolins NE (2012) Packaging of fat: an evolving model of lipid droplet assembly and expansion. J Biol Chem 287:2273–2279

    Article  CAS  PubMed  Google Scholar 

  • Brown JM, Chung S, Sawyer JK, Degirolamo C, Alger HM, Nguyen T, Zhu X, Duong MN, Wibley AL, Shah R, Davis MA, Kelley K, Wilson MD, Kent C, Parks JS, Rudel LL (2008) Inhibition of stearoyl-coenzyme A desaturase 1 dissociates insulin resistance and obesity from atherosclerosis. Circulation 118:1467–1475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buhman KK, Chen HC, Farese RV Jr (2001) The enzymes of neutral lipid synthesis. J Biol Chem 276:40369–40372

    Article  CAS  PubMed  Google Scholar 

  • Cao J, Dai DL, Yao L, Yu HH, Ning B, Zhang Q, Chen J, Cheng WH, Shen W, Yang ZX (2012) Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway. Mol Cell Biochem 364:115–129

    Article  CAS  PubMed  Google Scholar 

  • Capanni M, Calella F, Biagini MR, Genise S, Raimondi L, Bedogni G, Svegliati-Baroni G, Sofi F, Milani S, Abbate R, Surrenti C, Casini A (2006) Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 23:1143–1151

    Article  CAS  PubMed  Google Scholar 

  • Caviglia JM, Gayet C, Ota T, Hernandez-Ono A, Conlon DM, Jiang H, Fisher EA, Ginsberg HN (2011) Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy. J Lipid Res 52:1636–1651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chakravarthy MV, Pan Z, Zhu Y, Tordjman K, Schneider JG, Coleman T, Turk J, Semenkovich CF (2005) “New” hepatic fat activates PPARalpha to maintain glucose, lipid, and cholesterol homeostasis. Cell Metab 1:309–322

    Article  CAS  PubMed  Google Scholar 

  • Chavez JA, Summers SA (2012) A ceramide-centric view of insulin resistance. Cell Metab 15:585–594

    Article  CAS  PubMed  Google Scholar 

  • Choi CS, Savage DB, Kulkarni A, Yu XX, Liu ZX, Morino K, Kim S, Distefano A, Samuel VT, Neschen S, Zhang D, Wang A, Zhang XM, Kahn M, Cline GW, Pandey SK, Geisler JG, Bhanot S, Monia BP, Shulman GI (2007) Suppression of diacylglycerol acyltransferase-2 (DGAT2), but not DGAT1, with antisense oligonucleotides reverses diet-induced hepatic steatosis and insulin resistance. J Biol Chem 282:22678–22688

    Article  CAS  PubMed  Google Scholar 

  • Cohen JC, Horton JD, Hobbs HH (2011) Human fatty liver disease: old questions and new insights. Science 332:1519–1523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coleman RA, Mashek DG (2011) Mammalian triacylglycerol metabolism: synthesis, lipolysis, and signaling. Chem Rev 111:6359–6386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crespo J, Cayon A, Fernandez-Gil P, Hernandez-Guerra M, Mayorga M, Dominguez-Diez A, Fernandez-Escalante JC, Pons-Romero F (2001) Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 34:1158–1163

    Article  CAS  PubMed  Google Scholar 

  • Day CP, James OF (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114:842–845

    Article  CAS  PubMed  Google Scholar 

  • Dentin R, Benhamed F, Pegorier JP, Foufelle F, Viollet B, Vaulont S, Girard J, Postic C (2005) Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation. J Clin Invest 115:2843–2854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dentin R, Benhamed F, Hainault I, Fauveau V, Foufelle F, Dyck JR, Girard J, Postic C (2006) Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice. Diabetes 55:2159–2170

    Article  CAS  PubMed  Google Scholar 

  • Diraison F, Moulin P, Beylot M (2003) Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease. Diabetes Metab 29:478–485

    Article  CAS  PubMed  Google Scholar 

  • Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115:1343–1351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dorn C, Riener MO, Kirovski G, Saugspier M, Steib K, Weiss TS, Gabele E, Kristiansen G, Hartmann A, Hellerbrand C (2010) Expression of fatty acid synthase in nonalcoholic fatty liver disease. Int J Clin Exp Pathol 3:505–514

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ducheix S, Montagner A, Theodorou V, Ferrier L, Guillou H (2013) The liver X receptor: a master regulator of the gut-liver axis and a target for non alcoholic fatty liver disease. Biochem Pharmacol 86:96–105

    Article  CAS  PubMed  Google Scholar 

  • Endo M, Masaki T, Seike M, Yoshimatsu H (2007) TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c). Exp Biol Med (Maywood) 232:614–621

    CAS  Google Scholar 

  • Fabbrini E, Sullivan S, Klein S (2010) Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 51:679–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farese RV Jr, Walther TC (2009) Lipid droplets finally get a little R-E-S-P-E-C.-T. Cell 139:855–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fatima A, Waters S, O’Boyle P, Seoighe C, Morris DG (2014) Alterations in hepatic miRNA expression during negative energy balance in postpartum dairy cattle. BMC Genomics 15:28

    Article  PubMed  PubMed Central  Google Scholar 

  • Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, Marks AR, Ron D, Tabas I (2003) The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 5:781–792

    Article  CAS  PubMed  Google Scholar 

  • Flowers MT, Ntambi JM (2008) Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr Opin Lipidol 19:248–256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frangioudakis G, Burchfield JG, Narasimhan S, Cooney GJ, Leitges M, Biden TJ, Schmitz-Peiffer C (2009) Diverse roles for protein kinase C delta and protein kinase C epsilon in the generation of high-fat-diet-induced glucose intolerance in mice: regulation of lipogenesis by protein kinase C delta. Diabetologia 52:2616–2620

    Article  CAS  PubMed  Google Scholar 

  • Fromenty B, Robin MA, Igoudjil A, Mansouri A, Pessayre D (2004) The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab 30:121–138

    Article  CAS  PubMed  Google Scholar 

  • Fu S, Watkins SM, Hotamisligil GS (2012) The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling. Cell Metab 15:623–634

    Article  CAS  PubMed  Google Scholar 

  • Fujii H, Ikura Y, Arimoto J, Sugioka K, Iezzoni JC, Park SH, Naruko T, Itabe H, Kawada N, Caldwell SH, Ueda M (2009) Expression of perilipin and adipophilin in nonalcoholic fatty liver disease; relevance to oxidative injury and hepatocyte ballooning. J Atheroscler Thromb 16:893–901

    Article  CAS  PubMed  Google Scholar 

  • Galbo T, Perry RJ, Jurczak MJ, Camporez JP, Alves TC, Kahn M, Guigni BA, Serr J, Zhang D, Bhanot S, Samuel VT, Shulman GI (2013) Saturated and unsaturated fat induce hepatic insulin resistance independently of TLR-4 signaling and ceramide synthesis in vivo. Proc Natl Acad Sci U S A 110:12780–12785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gormaz JG, Rodrigo R, Videla LA, Beems M (2010) Biosynthesis and bioavailability of long-chain polyunsaturated fatty acids in non-alcoholic fatty liver disease. Prog Lipid Res 49:407–419

    Article  CAS  PubMed  Google Scholar 

  • Griffett K, Solt LA, El-Gendy Bel D, Kamenecka TM, Burris TP (2013) A liver-selective LXR inverse agonist that suppresses hepatic steatosis. ACS Chem Biol 8:559–567

    Article  CAS  PubMed  Google Scholar 

  • Guo Y, Cordes KR, Farese RV Jr, Walther TC (2009) Lipid droplets at a glance. J Cell Sci 122:749–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hannah VC, Ou J, Luong A, Goldstein JL, Brown MS (2001) Unsaturated fatty acids down-regulate srebp isoforms 1a and 1c by two mechanisms in HEK-293 cells. J Biol Chem 276:4365–4372

    Article  CAS  PubMed  Google Scholar 

  • Higuchi N, Kato M, Shundo Y, Tajiri H, Tanaka M, Yamashita N, Kohjima M, Kotoh K, Nakamuta M, Takayanagi R, Enjoji M (2008) Liver X receptor in cooperation with SREBP-1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease. Hepatol Res 38:1122–1129

    Article  CAS  PubMed  Google Scholar 

  • Hooper AJ, Adams LA, Burnett JR (2011) Genetic determinants of hepatic steatosis in man. J Lipid Res 52:593–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue M, Ohtake T, Motomura W, Takahashi N, Hosoki Y, Miyoshi S, Suzuki Y, Saito H, Kohgo Y, Okumura T (2005) Increased expression of PPARgamma in high fat diet-induced liver steatosis in mice. Biochem Biophys Res Commun 336:215–222

    Article  CAS  PubMed  Google Scholar 

  • Jacquier N, Choudhary V, Mari M, Toulmay A, Reggiori F, Schneiter R (2011) Lipid droplets are functionally connected to the endoplasmic reticulum in Saccharomyces cerevisiae. J Cell Sci 124:2424–2437

    Article  CAS  PubMed  Google Scholar 

  • Jacquier N, Mishra S, Choudhary V, Schneiter R (2013) Expression of oleosin and perilipins in yeast promotes formation of lipid droplets from the endoplasmic reticulum. J Cell Sci 126:5198–5209

    Article  CAS  PubMed  Google Scholar 

  • Kantartzis K, Machicao F, Machann J, Schick F, Fritsche A, Haring HU, Stefan N (2009) The DGAT2 gene is a candidate for the dissociation between fatty liver and insulin resistance in humans. Clin Sci (Lond) 116:531–537

    Article  CAS  Google Scholar 

  • Kanuri G, Bergheim I (2013) In vitro and in vivo models of non-alcoholic fatty liver disease (NAFLD). Int J Mol Sci 14:11963–11980

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaplowitz N, Ji C (2006) Unfolding new mechanisms of alcoholic liver disease in the endoplasmic reticulum. J Gastroenterol Hepatol 21(Suppl 3):S7–S9

    Article  CAS  PubMed  Google Scholar 

  • Kersten S (2001) Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep 2:282–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kessler SM, Simon Y, Gemperlein K, Gianmoena K, Cadenas C, Zimmer V, Pokorny J, Barghash A, Helms V, VAN Rooijen N, Bohle RM, Lammert F, Hengstler JG, Mueller R, Haybaeck J, Kiemer AK (2014) Fatty acid elongation in non-alcoholic steatohepatitis and hepatocellular carcinoma. Int J Mol Sci 15:5762–5773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohjima M, Enjoji M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, Fujino T, Yada M, Yada R, Harada N, Takayanagi R, Nakamuta M (2007) Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med 20:351–358

    CAS  PubMed  Google Scholar 

  • Kohlwein SD, Veenhuis M, van der Klei IJ (2013) Lipid droplets and peroxisomes: key players in cellular lipid homeostasis or a matter of fat—store ’em up or burn ’em down. Genetics 193:1–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kotronen A, Seppanen-Laakso T, Westerbacka J, Kiviluoto T, Arola J, Ruskeepaa AL, Oresic M, Yki-Jarvinen H (2009) Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver. Diabetes 58:203–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lambert JE, Ramos-Roman MA, Browning JD, Parks EJ (2014) Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology 146:726–735

    Article  CAS  PubMed  Google Scholar 

  • Larter CZ, Yeh MM, Williams J, Bell-Anderson KS, Farrell GC (2008) MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes. J Hepatol 49:407–416

    Article  CAS  PubMed  Google Scholar 

  • Lee JJ, Lambert JE, Hovhannisyan Y, Ramos-Roman MA, Trombold JR, Wagner DA, Parks EJ (2015) Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis. Am J Clin Nutr 101:34–43

    Article  CAS  PubMed  Google Scholar 

  • Lenihan-Geels G, Bishop KS, Ferguson LR (2013) Alternative sources of omega-3 fats: can we find a sustainable substitute for fish? Nutrients 5:1301–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Diehl AM (2003) Innate immunity in the liver. Curr Opin Gastroenterol 19:565–571

    Article  PubMed  Google Scholar 

  • Li ZZ, Berk M, McIntyre TM, Feldstein AE (2009) Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem 284:5637–5644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr, Ory DS, Schaffer JE (2003) Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A 100:3077–3082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lodhi IJ, Wei X, Semenkovich CF (2011) Lipoexpediency: de novo lipogenesis as a metabolic signal transmitter. Trends Endocrinol Metab 22:1–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Long AP, Manneschmidt AK, Verbrugge B, Dortch MR, Minkin SC, Prater KE, Biggerstaff JP, Dunlap JR, Dalhaimer P (2012) Lipid droplet de novo formation and fission are linked to the cell cycle in fission yeast. Traffic 13:705–714

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Vicario C, Gonzalez-Periz A, Rius B, Moran-Salvador E, Garcia-Alonso V, Lozano JJ, Bataller R, Cofan M, Kang JX, Arroyo V, Claria J, Titos E (2014) Molecular interplay between Delta5/Delta6 desaturases and long-chain fatty acids in the pathogenesis of non-alcoholic steatohepatitis. Gut 63:344–355

    Article  CAS  PubMed  Google Scholar 

  • Mao J, Demayo FJ, Li H, Abu-Elheiga L, Gu Z, Shaikenov TE, Kordari P, Chirala SS, Heird WC, Wakil SJ (2006) Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proc Natl Acad Sci U S A 103:8552–8557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin S, Parton RG (2006) Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol Cell Biol 7:373–378

    Article  CAS  PubMed  Google Scholar 

  • Matsusue K, Kusakabe T, Noguchi T, Takiguchi S, Suzuki T, Yamano S, Gonzalez FJ (2008) Hepatic steatosis in leptin-deficient mice is promoted by the PPARgamma target gene Fsp27. Cell Metab 7:302–311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuzaka T, Shimano H (2011) Molecular mechanisms involved in hepatic steatosis and insulin resistance. J Diabetes Investig 2:170–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuzaka T, Atsumi A, Matsumori R, Nie T, Shinozaki H, Suzuki-Kemuriyama N, Kuba M, Nakagawa Y, Ishii K, Shimada M, Kobayashi K, Yatoh S, Takahashi A, Takekoshi K, Sone H, Yahagi N, Suzuki H, Murata S, Nakamuta M, Yamada N, Shimano H (2012) Elovl6 promotes nonalcoholic steatohepatitis. Hepatology 56:2199–2208

    Article  CAS  PubMed  Google Scholar 

  • Mauvoisin D, Mounier C (2011) Hormonal and nutritional regulation of SCD1 gene expression. Biochimie 93:78–86

    Article  CAS  PubMed  Google Scholar 

  • Milic S, Stimac D (2012) Nonalcoholic fatty liver disease/steatohepatitis: epidemiology, pathogenesis, clinical presentation and treatment. Dig Dis 30:158–162

    Article  PubMed  Google Scholar 

  • Miyazaki M, Kim YC, Ntambi JM (2001) A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. J Lipid Res 42:1018–1024

    CAS  PubMed  Google Scholar 

  • Miyazaki M, Dobrzyn A, Man WC, Chu K, Sampath H, Kim HJ, Ntambi JM (2004) Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J Biol Chem 279:25164–25171

    Article  CAS  PubMed  Google Scholar 

  • Miyazaki M, Flowers MT, Sampath H, Chu K, Otzelberger C, Liu X, Ntambi JM (2007) Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. Cell Metab 6:484–496

    Article  CAS  PubMed  Google Scholar 

  • Moon YA, Shah NA, Mohapatra S, Warrington JA, Horton JD (2001) Identification of a mammalian long chain fatty acyl elongase regulated by sterol regulatory element-binding proteins. J Biol Chem 276:45358–45366

    Article  CAS  PubMed  Google Scholar 

  • Moon YA, Ochoa CR, Mitsche MA, Hammer RE, Horton JD (2014) Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance. J Lipid Res 55:2597–2605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moore JB, Gunn PJ, Fielding BA (2014) The role of dietary sugars and de novo lipogenesis in non-alcoholic fatty liver disease. Nutrients 6:5679–5703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Motomura W, Inoue M, Ohtake T, Takahashi N, Nagamine M, Tanno S, Kohgo Y, Okumura T (2006) Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet. Biochem Biophys Res Commun 340:1111–1118

    Article  CAS  PubMed  Google Scholar 

  • Musso G, Gambino R, Cassader M, Pagano G (2011) Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 43:617–649

    Article  PubMed  Google Scholar 

  • Nagaya T, Tanaka N, Suzuki T, Sano K, Horiuchi A, Komatsu M, Nakajima T, Nishizawa T, Joshita S, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Nakayama J, Tanaka E, Aoyama T (2010) Down-regulation of SREBP-1c is associated with the development of burned-out NASH. J Hepatol 53:724–731

    Article  CAS  PubMed  Google Scholar 

  • Nakamura MT, Nara TY (2004) Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu Rev Nutr 24:345–376

    Article  CAS  PubMed  Google Scholar 

  • Neuschwander-Tetri BA, Caldwell SH (2003) Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 37:1202–1219

    Article  PubMed  Google Scholar 

  • Nobili V, Alisi A, Della Corte C, Rise P, Galli C, Agostoni C, Bedogni G (2013) Docosahexaenoic acid for the treatment of fatty liver: randomised controlled trial in children. Nutr Metab Cardiovasc Dis 23:1066–1070

    Article  CAS  PubMed  Google Scholar 

  • Ntambi JM, Miyazaki M, Stoehr JP, Lan H, Kendziorski CM, Yandell BS, Song Y, Cohen P, Friedman JM, Attie AD (2002) Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci U S A 99:11482–11486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nye CK, Hanson RW, Kalhan SC (2008) Glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat. J Biol Chem 283:27565–27574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, Subramanian V, Mukundan L, Ferrante AW, Chawla A (2008) Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 7:496–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peter A, Cegan A, Wagner S, Elcnerova M, Konigsrainer A, Konigsrainer I, Haring HU, Schleicher ED, Stefan N (2011) Relationships between hepatic stearoyl-CoA desaturase-1 activity and mRNA expression with liver fat content in humans. Am J Physiol Endocrinol Metab 300:E321–E326

    Article  CAS  PubMed  Google Scholar 

  • Petersson H, Arnlov J, Zethelius B, Riserus U (2010) Serum fatty acid composition and insulin resistance are independently associated with liver fat markers in elderly men. Diabetes Res Clin Pract 87:379–384

    Article  CAS  PubMed  Google Scholar 

  • Pettinelli P, del Pozo T, Araya J, Rodrigo R, Araya AV, Smok G, Csendes A, Gutierrez L, Rojas J, Korn O, Maluenda F, Diaz JC, Rencoret G, Braghetto I, Castillo J, Poniachik J, Videla LA (2009) Enhancement in liver SREBP-1c/PPAR-alpha ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. Biochim Biophys Acta 1792:1080–1086

    Article  CAS  PubMed  Google Scholar 

  • Postic C, Girard J (2008) Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 118:829–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Puri P, Mirshahi F, Cheung O, Natarajan R, Maher JW, Kellum JM, Sanyal AJ (2008) Activation and dysregulation of the unfolded protein response in nonalcoholic fatty liver disease. Gastroenterology 134:568–576

    Article  CAS  PubMed  Google Scholar 

  • Robertson G, Leclercq I, Farrell GC (2001) Nonalcoholic steatosis and steatohepatitis. II. Cytochrome P-450 enzymes and oxidative stress. Am J Physiol Gastrointest Liver Physiol 281:G1135–G1139

    CAS  PubMed  Google Scholar 

  • Rolo AP, Teodoro JS, Palmeira CM (2012) Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic Biol Med 52:59–69

    Article  CAS  PubMed  Google Scholar 

  • Rui L (2014) Energy metabolism in the liver. Compr Physiol 4:177–197

    Article  PubMed  PubMed Central  Google Scholar 

  • Sampath H, Ntambi JM (2006) Stearoyl-coenzyme A desaturase 1, sterol regulatory element binding protein-1c and peroxisome proliferator-activated receptor-alpha: independent and interactive roles in the regulation of lipid metabolism. Curr Opin Clin Nutr Metab Care 9:84–88

    Article  CAS  PubMed  Google Scholar 

  • Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI (2004) Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 279:32345–32353

    Article  CAS  PubMed  Google Scholar 

  • Samuel VT, Liu ZX, Wang A, Beddow SA, Geisler JG, Kahn M, Zhang XM, Monia BP, Bhanot S, Shulman GI (2007) Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J Clin Invest 117:739–745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samuel VT, Petersen KF, Shulman GI (2010) Lipid-induced insulin resistance: unravelling the mechanism. Lancet 375:2267–2277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen L, Cui A, Xue Y, Cui Y, Dong X, Gao Y, Yang H, Fang F, Chang Y (2014) Hepatic differentiated embryo-chondrocyte-expressed gene 1 (Dec1) inhibits sterol regulatory element-binding protein-1c (Srebp-1c) expression and alleviates fatty liver phenotype. J Biol Chem 289:23332–23342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silbernagel G, Kovarova M, Cegan A, Machann J, Schick F, Lehmann R, Haring HU, Stefan N, Schleicher E, Fritsche A, Peter A (2012) High hepatic SCD1 activity is associated with low liver fat content in healthy subjects under a lipogenic diet. J Clin Endocrinol Metab 97:E2288–E2292

    Article  CAS  PubMed  Google Scholar 

  • Sim WC, Park S, Lee KY, Je YT, Yin HQ, Choi YJ, Sung SH, Park SJ, Park HJ, Shin KJ, Lee BH (2014) LXR-alpha antagonist meso-dihydroguaiaretic acid attenuates high-fat diet-induced nonalcoholic fatty liver. Biochem Pharmacol 90:414–424

    Article  CAS  PubMed  Google Scholar 

  • Spadaro L, Magliocco O, Spampinato D, Piro S, Oliveri C, Alagona C, Papa G, Rabuazzo AM, Purrello F (2008) Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Dig Liver Dis 40:194–199

    Article  CAS  PubMed  Google Scholar 

  • Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, Palmer CD, Gudnason V, Eiriksdottir G, Garcia ME, Launer LJ, Nalls MA, Clark JM, Mitchell BD, Shuldiner AR, Butler JL, Tomas M, Hoffmann U, Hwang SJ, Massaro JM, O’Donnell CJ, Sahani DV, Salomaa V, Schadt EE, Schwartz SM, Siscovick DS, Voight BF, Carr JJ, Feitosa MF, Harris TB, Fox CS, Smith AV, Kao WH, Hirschhorn JN, Borecki IB (2011) Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 7:e1001324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stefan N, Haring HU (2011) The metabolically benign and malignant fatty liver. Diabetes 60:2011–2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stefan N, Peter A, Cegan A, Staiger H, Machann J, Schick F, Claussen CD, Fritsche A, Haring HU, Schleicher E (2008) Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans. Diabetologia 51:648–656

    Article  CAS  PubMed  Google Scholar 

  • St-Jules DE, Watters CA, Brunt EM, Wilkens LR, Novotny R, Belt P, Lavine JE (2013) Estimation of fish and omega-3 fatty acid intake in pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 57:627–633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strable MS, Ntambi JM (2010) Genetic control of de novo lipogenesis: role in diet-induced obesity. Crit Rev Biochem Mol Biol 45:199–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Straub BK, Stoeffel P, Heid H, Zimbelmann R, Schirmacher P (2008) Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis. Hepatology 47:1936–1946

    Article  CAS  PubMed  Google Scholar 

  • Teli MR, James OF, Burt AD, Bennett MK, Day CP (1995) The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology 22:1714–1719

    Article  CAS  PubMed  Google Scholar 

  • Tovar AR, Torre-Villalvazo I, Ochoa M, Elias AL, Ortiz V, Aguilar-Salinas CA, Torres N (2005) Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats. J Lipid Res 46:1823–1832

    Article  CAS  PubMed  Google Scholar 

  • Vega RB, Huss JM, Kelly DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20:1868–1876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vessby B, Gustafsson IB, Tengblad S, Boberg M, Andersson A (2002) Desaturation and elongation of fatty acids and insulin action. Ann N Y Acad Sci 967:183–195

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Wang D, Topczewski F, Pagliassotti MJ (2006) Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 291:E275–E281

    Article  CAS  PubMed  Google Scholar 

  • Wilfling F, Haas JT, Walther TC, Farese RV Jr (2014) Lipid droplet biogenesis. Curr Opin Cell Biol 29:39–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu T, Liu YH, Fu YC, Liu XM, Zhou XH (2014) Direct evidence of sirtuin downregulation in the liver of non-alcoholic fatty liver disease patients. Ann Clin Lab Sci 44:410–418

    CAS  PubMed  Google Scholar 

  • Yahagi N, Shimano H, Hasty AH, Matsuzaka T, Ide T, Yoshikawa T, Amemiya-Kudo M, Tomita S, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Nagai R, Ishibashi S, Yamada N (2002) Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice. J Biol Chem 277:19353–19357

    Article  CAS  PubMed  Google Scholar 

  • Yamada M, Wolfe D, Han G, French SW, Ross MG, Desai M (2011) Early onset of fatty liver in growth-restricted rat fetuses and newborns. Congenit Anom (Kyoto) 51:167–173

    Article  CAS  Google Scholar 

  • Yamada K, Mizukoshi E, Sunagozaka H, Arai K, Yamashita T, Takeshita Y, Misu H, Takamura T, Kitamura S, Zen Y, Nakanuma Y, Honda M, Kaneko S (2015) Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis. Liver Int 35:582–590

    Article  CAS  PubMed  Google Scholar 

  • Yamazaki Y, Usui I, Kanatani Y, Matsuya Y, Tsuneyama K, Fujisaka S, Bukhari A, Suzuki H, Senda S, Imanishi S, Hirata K, Ishiki M, Hayashi R, Urakaze M, Nemoto H, Kobayashi M, Tobe K (2009) Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice. Am J Physiol Endocrinol Metab 297:E1179–E1186

    Article  CAS  PubMed  Google Scholar 

  • Yki-Jarvinen H (2014) Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2:901–910

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Département des Sciences Biologiques, Centre de recherche BioMed, Université du Québec à Montréal, Case Postale 8888 Succursale Centre-ville, Montréal, QC, Canada, H3C 3P8

    Mohamed Amine Lounis, Sabri Rial & Catherine Mounier

  2. Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA

    James M. Ntambi

  3. Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA

    James M. Ntambi

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  1. Mohamed Amine Lounis
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  2. Sabri Rial
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  4. Catherine Mounier
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Correspondence to Catherine Mounier .

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  1. Departments of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA

    James M. Ntambi

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Lounis, M.A., Rial, S., Ntambi, J.M., Mounier, C. (2016). Role of Lipogenesis and Lipid Desaturases in Non-alcoholic Fatty Liver Disease. In: Ntambi, J. (eds) Hepatic De Novo Lipogenesis and Regulation of Metabolism. Springer, Cham. https://doi.org/10.1007/978-3-319-25065-6_7

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