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Hepatic Lipogenesis: Nutritional Control and Pathophysiological Relevance

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Hepatic De Novo Lipogenesis and Regulation of Metabolism

Abstract

Hepatic de novo lipogenesis (DNL) is important in generating various fatty acids to meet the needs of cellular functions such as cell membrane structural composition and molecular signaling. Like many cellular processes, hepatic DNL is tightly regulated by different dietary nutrient composition and hormonal fluctuation. For example, dietary glucose and fructose could act as a substrate for DNL; insulin together with the stimulation of glucose could induce signaling to enhance hepatic DNL, while glucagon has an inhibitory effect on hepatic DNL. However, the dysregulation of hepatic DNL could lead to metabolic disorders such as non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). In this article, nutrient composition and hormonal regulation of hepatic DNL, as well as the implication of hepatic DNL in contributing to metabolic diseases will be discussed in detail.

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References

  • Abu-Elheiga L, Matzuk MM, Kordari P, Oh W, Shaikenov T, Gu Z, Wakil SJ (2005) Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal. Proc Natl Acad Sci U S A 102:12011–12016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Acheson KJ, Schutz Y, Bessard T, Ravussin E, Jequier E, Flatt JP (1984) Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal. Am J Physiol 246:E62–E70

    CAS  PubMed  Google Scholar 

  • Acheson KJ, Schutz Y, Bessard T, Anantharaman K, Flatt JP, Jequier E (1988) Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am J Clin Nutr 48:240–247

    CAS  PubMed  Google Scholar 

  • Adiels M, Olofsson SO, Taskinen MR, Boren J (2008) Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arterioscler Thromb Vasc Biol 28:1225–1236

    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 

  • Amemiya-Kudo M, Shimano H, Hasty AH, Yahagi N, Yoshikawa T, Matsuzaka T, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Sato R, Kimura S, Ishibashi S, Yamada N (2002) Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes. J Lipid Res 43:1220–1235

    CAS  PubMed  Google Scholar 

  • Baker AL, Rosenberg IH (1987) Hepatic complications of total parenteral nutrition. Am J Med 82:489–497

    Article  CAS  PubMed  Google Scholar 

  • Barber MC, Price NT, Travers MT (2005) Structure and regulation of acetyl-CoA carboxylase genes of metazoa. Biochim Biophys Acta 1733:1–28

    Article  CAS  PubMed  Google Scholar 

  • Basciano H, Federico L, Adeli K (2005) Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond) 2:5

    Article  CAS  Google Scholar 

  • Beg ZH, Allmann DW, Gibson DM (1973) Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and wth protein fractions of rat liver cytosol. Biochem Biophys Res Commun 54:1362–1369

    Article  CAS  PubMed  Google Scholar 

  • Berglund ED, Lee-Young RS, Lustig DG, Lynes SE, Donahue EP, Camacho RC, Meredith ME, Magnuson MA, Charron MJ, Wasserman DH (2009) Hepatic energy state is regulated by glucagon receptor signaling in mice. J Clin Invest 119:2412–2422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beynen AC, Vaartjes WJ, Geelen MJ (1979) Opposite effects of insulin and glucagon in acute hormonal control of hepatic lipogenesis. Diabetes 28:828–835

    Article  CAS  PubMed  Google Scholar 

  • Beynen AC, Vaartjes WJ, Geelen MJ (1980) Acute effects of insulin on fatty acid metabolism in isolated rat hepatocytes. Horm Metab Res 12:425–430

    Article  CAS  PubMed  Google Scholar 

  • Beynen AC, Haagsman HP, Van Golde LM, Geelen MJ (1981) The effects of insulin and glucagon on the release of triacylglycerols by isolated rat hepatocytes are mere reflections of the hormonal effects on the rate of triacylglycerol synthesis. Biochim Biophys Acta 665:1–7

    Article  CAS  PubMed  Google Scholar 

  • Biddinger SB, Hernandez-Ono A, Rask-Madsen C, Haas JT, Aleman JO, Suzuki R, Scapa EF, Agarwal C, Carey MC, Stephanopoulos G, Cohen DE, King GL, Ginsberg HN, Kahn CR (2008) Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metab 7:125–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bray GA (2013) Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people. Adv Nutr 4:220–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown MS, Goldstein JL (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89:331–340

    Article  CAS  PubMed  Google Scholar 

  • Brown MS, Goldstein JL (2008) Selective versus total insulin resistance: a pathogenic paradox. Cell Metab 7:95–96

    Article  CAS  PubMed  Google Scholar 

  • Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brownsey RW, Boone AN, Elliott JE, Kulpa JE, Lee WM (2006) Regulation of acetyl-CoA carboxylase. Biochem Soc Trans 34:223–227

    Article  CAS  PubMed  Google Scholar 

  • Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS (2008) Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 134:933–944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Capeau J (2008) Insulin resistance and steatosis in humans. Diabetes Metab 34:649–657

    Article  CAS  PubMed  Google Scholar 

  • Carlson CA, Kim KH (1973) Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem 248:378–380

    CAS  PubMed  Google Scholar 

  • Carlson CL, Winder WW (1999) Liver AMP-activated protein kinase and acetyl-CoA carboxylase during and after exercise. J Appl Physiol 86:669–674

    CAS  PubMed  Google Scholar 

  • Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55:2005–2023

    Article  PubMed  Google Scholar 

  • Chen G, Liang G, Ou J, Goldstein JL, Brown MS (2004) Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci U S A 101:11245–11250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chong MF, Fielding BA, Frayn KN (2007) Mechanisms for the acute effect of fructose on postprandial lipemia. Am J Clin Nutr 85:1511–1520

    CAS  PubMed  Google Scholar 

  • Clarke SD, Jump DB (1996) Polyunsaturated fatty acid regulation of hepatic gene transcription. J Nutr 126:1105S–1109S

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Dirlewanger M, Schneiter P, Jequier E, Tappy L (2000) Effects of fructose on hepatic glucose metabolism in humans. Am J Physiol Endocrinol Metab 279:E907–E911

    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 

  • Fabbrini E, Mohammed BS, Magkos F, Korenblat KM, Patterson BW, Klein S (2008) Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology 134:424–431

    Article  CAS  PubMed  Google Scholar 

  • Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43:S99–S112

    Article  CAS  PubMed  Google Scholar 

  • Feller DD (1954) Metabolism of adipose tissue. I. Incorporation of acetate carbon into lipides by slices of adipose tissue. J Biol Chem 206:171–180

    CAS  PubMed  Google Scholar 

  • Flick PK, Chen J, Vagelos PR (1977) Effect of dietary linoleate on synthesis and degradation of fatty acid synthetase from rat liver. J Biol Chem 252:4242–4249

    CAS  PubMed  Google Scholar 

  • Gao B, Bataller R (2011) Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 141:1572–1585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garrido G, Guzman M, Odriozola JM (1996) Effect of different types of high carbohydrate diets on glycogen metabolism in liver and skeletal muscle of endurance-trained rats. Eur J Appl Physiol Occup Physiol 74:91–99

    Article  CAS  PubMed  Google Scholar 

  • Geelen MJ, Gibson DM (1975) Lipogenesis in maintenance cultures of rat hepatocytes. FEBS Lett 58:334–339

    Article  CAS  PubMed  Google Scholar 

  • Geelen MJ, Vaartjes WJ (1977) Levels of cyclic 3′-5′-adenosine monophosphate (cAMP) in maintenance cultures of rat hepatocytes in response to insulin and glucagon. Lipids 12:577–580

    Article  CAS  PubMed  Google Scholar 

  • Geelen MJ, Beynen AC, Christiansen RZ, Lepreau-Jose MJ, Gibson DM (1978) Short-term effects of insulin and glucagon on lipid synthesis in isolated rat hepatocytes. Covariance of acetyl-CoA carboxylase activity and the rate of 3H2O incorporation into fatty acids. FEBS Lett 95:326–330

    Article  CAS  PubMed  Google Scholar 

  • Gibbons GF (1990) Assembly and secretion of hepatic very-low-density lipoprotein. Biochem J 268:1–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gibbons GF, Burnham FJ (1991) Effect of nutritional state on the utilization of fatty acids for hepatitic triacylglycerol synthesis and secretion as very-low-density lipoprotein. Biochem J 275(Pt 1):87–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldstein JL, Brown MS (2009) The LDL receptor. Arterioscler Thromb Vasc Biol 29:431–438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gorski J, Oscai LB, Palmer WK (1990) Hepatic lipid metabolism in exercise and training. Med Sci Sports Exerc 22:213–221

    CAS  PubMed  Google Scholar 

  • Grahame Hardie D (2014) AMP-activated protein kinase: a key regulator of energy balance with many roles in human disease. J Intern Med 276:543–559

    Article  CAS  PubMed  Google Scholar 

  • Grundy SM (1998) Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome. Am J Cardiol 81:18B–25B

    Article  CAS  PubMed  Google Scholar 

  • Guo X, Li H, Xu H, Halim V, Zhang W, Wang H, Ong KT, Woo SL, Walzem RL, Mashek DG, Dong H, Lu F, Wei L, Huo Y, Wu C (2012) Palmitoleate induces hepatic steatosis but suppresses liver inflammatory response in mice. PLoS One 7, e39286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haeusler RA, Accili D (2008) The double life of Irs. Cell Metab 8:7–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris RA, Mapes JP, Ochs RS, Crabb DW, Stropes L (1979) Hormonal control of hepatic lipogenesis. Adv Exp Med Biol 111:17–42

    Article  CAS  PubMed  Google Scholar 

  • Hausberger FX, Milstein SW, Rutman RJ (1954) The influence of insulin on glucose utilization in adipose and hepatic tissues in vitro. J Biol Chem 208:431–438

    CAS  PubMed  Google Scholar 

  • Havel PJ (2005) Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 63:133–157

    Article  PubMed  Google Scholar 

  • Hellerstein MK (1999) De novo lipogenesis in humans: metabolic and regulatory aspects. Eur J Clin Nutr 53(Suppl 1):S53–S65

    Article  PubMed  Google Scholar 

  • Hellerstein MK, Schwarz JM, Neese RA (1996) Regulation of hepatic de novo lipogenesis in humans. Annu Rev Nutr 16:523–557

    Article  CAS  PubMed  Google Scholar 

  • Herzberg GR (1983) The influence of dietary fatty acid composition on lipogenesis. Adv Nutr Res 5:221–253

    Article  CAS  PubMed  Google Scholar 

  • Holland R, Witters LA, Hardie DG (1984) Glucagon inhibits fatty acid synthesis in isolated hepatocytes via phosphorylation of acetyl-CoA carboxylase by cyclic-AMP-dependent protein kinase. Eur J Biochem 140:325–333

    Article  CAS  PubMed  Google Scholar 

  • Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109:1125–1131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huo Y, Guo X, Li H, Xu H, Halim V, Zhang W, Wang H, Fan YY, Ong KT, Woo SL, Chapkin RS, Mashek DG, Chen Y, Dong H, Lu F, Wei L, Wu C (2012) Targeted overexpression of inducible 6-phosphofructo-2-kinase in adipose tissue increases fat deposition but protects against diet-induced insulin resistance and inflammatory responses. J Biol Chem 287:21492–21500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ingle DL, Bauman DE, Garrigus US (1972) Lipogenesis in the ruminant: in vivo site of fatty acid synthesis in sheep. J Nutr 102:617–623

    CAS  PubMed  Google Scholar 

  • Institute of Medicine (US) Committee on Preventing the Global Epidemic of Cardiovascular Disease: Meeting the Challenges in Developing Countries, Fuster V, Kelly BB (eds) (2010) Promoting cardiovascular health in the developing world: a critical challenge to achieve global health. National Academies Press, Washington DC

    Google Scholar 

  • Ishii S, IIzuka K, Miller BC, Uyeda K (2004) Carbohydrate response element binding protein directly promotes lipogenic enzyme gene transcription. Proc Natl Acad Sci U S A 101:15597–15602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683–689

    Article  CAS  PubMed  Google Scholar 

  • Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A, Thompson MW, George J (2009) Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 50:1105–1112

    Article  CAS  PubMed  Google Scholar 

  • Kahn, R., Buse, J., Ferrannini, E., Stern, M., American Diabetes, A., and European Association for the Study of, D (2005) The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 28:2289–2304

    Article  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 

  • Kimball SR, Siegfried BA, Jefferson LS (2004) Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase. J Biol Chem 279:54103–54109

    Article  CAS  PubMed  Google Scholar 

  • Kornacker MS, Lowenstein JM (1965) Citrate and the conversion of carbohydrate into fat. The activities of citrate-cleavage enzyme and acetate thiokinase in livers of starved and re-fed rats. Biochem J 94:209–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubota N, Kubota T, Itoh S, Kumagai H, Kozono H, Takamoto I, Mineyama T, Ogata H, Tokuyama K, Ohsugi M, Sasako T, Moroi M, Sugi K, Kakuta S, Iwakura Y, Noda T, Ohnishi S, Nagai R, Tobe K, Terauchi Y, Ueki K, Kadowaki T (2008) Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding. Cell Metab 8:49–64

    Article  CAS  PubMed  Google Scholar 

  • Lakshmanan MR, Nepokroeff CM, Porter JW (1972) Control of the synthesis of fatty-acid synthetase in rat liver by insulin, glucagon, and adenosine 3′:5′cyclic monophosphate. Proc Natl Acad Sci U S A 69:3516–3519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lammert O, Grunnet N, Faber P, Bjornsbo KS, Dich J, Larsen LO, Neese RA, Hellerstein MK, Quistorff B (2000) Effects of isoenergetic overfeeding of either carbohydrate or fat in young men. Br J Nutr 84:233–245

    CAS  PubMed  Google Scholar 

  • Lancaster GI, Febbraio MA (2014) The immunomodulating role of exercise in metabolic disease. Trends Immunol 35:262–269

    Article  CAS  PubMed  Google Scholar 

  • Lee IM, Sesso HD, Oguma Y, Paffenbarger RS Jr (2004) The “weekend warrior” and risk of mortality. Am J Epidemiol 160:636–641

    Article  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 

  • Lefkowitch JH (2005) Morphology of alcoholic liver disease. Clin Liver Dis 9:37–53

    Article  PubMed  Google Scholar 

  • Lewis GF, Carpentier A, Adeli K, Giacca A (2002) Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23:201–229

    Article  CAS  PubMed  Google Scholar 

  • Li S, Brown MS, Goldstein JL (2010) Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci U S A 107:3441–3446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M (2011) AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab 13:376–388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liangpunsakul S, Ross RA, Crabb DW (2013) Activation of carbohydrate response element-binding protein by ethanol. J Investig Med 61:270–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liepa GU, Beitz DC, Linder JR (1978) Fatty acid synthesis in ruminating and nonruminating goats. J Nutr 108:1733–1739

    CAS  PubMed  Google Scholar 

  • Ljungstrom O, Ekman P (1977) Glucagon-induced phosphorylation of pyruvate kinase (type L) in rat liver slices. Biochem Biophys Res Commun 78:1147–1155

    Article  CAS  PubMed  Google Scholar 

  • Longuet C, Sinclair EM, Maida A, Baggio LL, Maziarz M, Charron MJ, Drucker DJ (2008) The glucagon receptor is required for the adaptive metabolic response to fasting. Cell Metab 8:359–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lynen F (1953) Functional group of coenzyme A and its metabolic relations, especially in the fatty acid cycle. Fed Proc 12:683–691

    CAS  PubMed  Google Scholar 

  • Lynen F, Knappe J, Lorch E, Juetting G, Ringelmann E, Lachance JP (1961) On the biochemical function of biotin. II. Purification and mode of action of beta-methyl-crotonyl-carboxylase. Biochem Z 335:123–167

    CAS  PubMed  Google Scholar 

  • Ma XM, Blenis J (2009) Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10:307–318

    Article  PubMed  CAS  Google Scholar 

  • Ma L, Tsatsos NG, Towle HC (2005) Direct role of ChREBP.Mlx in regulating hepatic glucose-responsive genes. J Biol Chem 280:12019–12027

    Article  CAS  PubMed  Google Scholar 

  • Marriott BP, Olsho L, Hadden L, Connor P (2010) Intake of added sugars and selected nutrients in the United States, National Health and Nutrition Examination Survey (NHANES) 2003-2006. Crit Rev Food Sci Nutr 50:228–258

    Article  CAS  PubMed  Google Scholar 

  • Masoro EJ, Chaikoff IL, Dauben WG (1949) Lipogenesis from glucose in the normal and liverless animal as studied with C14-labeled glucose. J Biol Chem 179:1117–1125

    CAS  PubMed  Google Scholar 

  • Matsumoto M, Han S, Kitamura T, Accili D (2006) Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism. J Clin Invest 116:2464–2472

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meshkani R, Adeli K (2009) Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clin Biochem 42:1331–1346

    Article  CAS  PubMed  Google Scholar 

  • Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–343

    Article  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 

  • Monetti M, Levin MC, Watt MJ, Sajan MP, Marmor S, Hubbard BK, Stevens RD, Bain JR, Newgard CB, Farese RV Sr, Hevener AL, Farese RV Jr (2007) Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab 6:69–78

    Article  CAS  PubMed  Google Scholar 

  • Muller P, Singh A, Orci L, Jeanrenaud B (1976) Secretory processes, carbohydrate and lipid metabolism in isolated mouse hepatocytes. Aspects of regulation by glucagon and insulin. Biochim Biophys Acta 428:480–494

    Article  CAS  PubMed  Google Scholar 

  • Muller A, Unthan-Fechner K, Probst I (1988) Activation of phosphofructokinase 2 by insulin in cultured hepatocytes without accompanying changes of effector levels or cAMP-stimulated protein kinase activity ratios. Eur J Biochem 176:415–420

    Article  CAS  PubMed  Google Scholar 

  • Munday MR (2002) Regulation of mammalian acetyl-CoA carboxylase. Biochem Soc Trans 30:1059–1064

    Article  CAS  PubMed  Google Scholar 

  • Musch K, Ojakian MA, Williams MA (1974) Comparison of alpha-linolenate and oleate in lowering activity of lipogenic enzymes in rat liver: evidence for a greater effect of dietary linoleinate independent of food and carbohydrate intake. Biochim Biophys Acta 337:343–348

    Article  CAS  PubMed  Google Scholar 

  • O’Doherty RM, Lehman DL, Telemaque-Potts S, Newgard CB (1999) Metabolic impact of glucokinase overexpression in liver: lowering of blood glucose in fed rats is accompanied by hyperlipidemia. Diabetes 48:2022–2027

    Article  PubMed  Google Scholar 

  • O’Shea RS, Dasarathy S, McCullough AJ, Practice Guideline Committee of the American Association for the Study of Liver Diseases, Practice Parameters Committee of the American College of Gastroenterology. (2010) Alcoholic liver disease. Hepatology 51:307–328

    Article  PubMed  Google Scholar 

  • Oh W, Abu-Elheiga L, Kordari P, Gu Z, Shaikenov T, Chirala SS, Wakil SJ (2005) Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2 knockout mice. Proc Natl Acad Sci U S A 102:1384–1389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olofsson SO, Boren J (2005) Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis. J Intern Med 258:395–410

    Article  CAS  PubMed  Google Scholar 

  • Park H, Kaushik VK, Constant S, Prentki M, Przybytkowski E, Ruderman NB, Saha AK (2002) Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J Biol Chem 277:32571–32577

    Article  CAS  PubMed  Google Scholar 

  • Pasquet P, Brigant L, Froment A, Koppert GA, Bard D, de Garine I, Apfelbaum M (1992) Massive overfeeding and energy balance in men: the Guru Walla model. Am J Clin Nutr 56:483–490

    CAS  PubMed  Google Scholar 

  • Pearce J (1983) Fatty acid synthesis in liver and adipose tissue. Proc Nutr Soc 42:263–271

    Article  CAS  PubMed  Google Scholar 

  • Petit JM, Guiu B, Duvillard L, Jooste V, Brindisi MC, Athias A, Bouillet B, Habchi M, Cottet V, Gambert P, Hillon P, Cercueil JP, Verges B (2012) Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a lower prevalence of steatosis in patients with type 2 diabetes. Clin Nutr 31(4):520–525

    Article  CAS  PubMed  Google Scholar 

  • Pollock NK, Bundy V, Kanto W, Davis CL, Bernard PJ, Zhu H, Gutin B, Dong Y (2012) Greater fructose consumption is associated with cardiometabolic risk markers and visceral adiposity in adolescents. J Nutr 142:251–257

    Article  CAS  PubMed  Google Scholar 

  • Rabol R, Petersen KF, Dufour S, Flannery C, Shulman GI (2011) Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc Natl Acad Sci U S A 108:13705–13709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rudack D, Chisholm EM, Holten D (1971a) Rat liver glucose 6-phosphate dehydrogenase. Regulation by carbohydrate diet and insulin. J Biol Chem 246:1249–1254

    CAS  PubMed  Google Scholar 

  • Rudack D, Gozukara EM, Chisholm EM, Holten D (1971b) The effect of dietary carbohydrate and fat on the synthesis of rat liver 6-phosphogluconate dehydrogenase. Biochim Biophys Acta 252:305–313

    Article  CAS  PubMed  Google Scholar 

  • Ruderman NB, Park H, Kaushik VK, Dean D, Constant S, Prentki M, Saha AK (2003) AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise. Acta Physiol Scand 178:435–442

    Article  CAS  PubMed  Google Scholar 

  • Sajan MP, Ivey RA, Lee MC, Farese RV (2015) Hepatic insulin resistance in ob/ob mice involves increases in ceramide, aPKC activity, and selective impairment of Akt-dependent FoxO1 phosphorylation. J Lipid Res 56:70–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salam WH, Wilcox HG, Heimberg M (1988) Effects of oleic acid on the biosynthesis of lipoprotein apoproteins and distribution into the very-low-density lipoprotein by the isolated perfused rat liver. Biochem J 251:809–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sampath H, Miyazaki M, Dobrzyn A, Ntambi JM (2007) Stearoyl-CoA desaturase-1 mediates the pro-lipogenic effects of dietary saturated fat. J Biol Chem 282:2483–2493

    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 

  • Schonfeld G, Pfleger B (1971) Utilization of exogenous free fatty acids for the production of very low density lipoprotein triglyceride by livers of carbohydrate-fed rats. J Lipid Res 12:614–621

    CAS  PubMed  Google Scholar 

  • Schwarz JM, Linfoot P, Dare D, Aghajanian K (2003) Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 77:43–50

    CAS  PubMed  Google Scholar 

  • Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS (1997) Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Invest 99:838–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimomura I, Matsuda M, Hammer RE, Bashmakov Y, Brown MS, Goldstein JL (2000) Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell 6:77–86

    Article  CAS  PubMed  Google Scholar 

  • Shojaee-Moradie F, Baynes KC, Pentecost C, Bell JD, Thomas EL, Jackson NC, Stolinski M, Whyte M, Lovell D, Bowes SB, Gibney J, Jones RH, Umpleby AM (2007) Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism. Diabetologia 50:404–413

    Article  CAS  PubMed  Google Scholar 

  • Shrago E, Glennon JA, Gordon ES (1971) Comparative aspects of lipogenesis in mammalian tissues. Metabolism 20:54–62

    Article  CAS  PubMed  Google Scholar 

  • Sim AT, Hardie DG (1988) The low activity of acetyl-CoA carboxylase in basal and glucagon-stimulated hepatocytes is due to phosphorylation by the AMP-activated protein kinase and not cyclic AMP-dependent protein kinase. FEBS Lett 233:294–298

    Article  CAS  PubMed  Google Scholar 

  • Sozio M, Crabb DW (2008) Alcohol and lipid metabolism. Am J Physiol Endocrinol Metab 295:E10–E16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sozio MS, Liangpunsakul S, Crabb D (2010) The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Semin Liver Dis 30:378–390

    Article  CAS  PubMed  Google Scholar 

  • Stanford KI, Goodyear LJ (2014) Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle. Adv Physiol Educ 38:308–314

    Article  PubMed  PubMed Central  Google Scholar 

  • Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W, McGahan JP, Seibert A, Krauss RM, Chiu S, Schaefer EJ, Ai M, Otokozawa S, Nakajima K, Nakano T, Beysen C, Hellerstein MK, Berglund L, Havel PJ (2009) Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 119:1322–1334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stillemark-Billton P, Beck C, Boren J, Olofsson SO (2005) Relation of the size and intracellular sorting of apoB to the formation of VLDL 1 and VLDL 2. J Lipid Res 46:104–114

    Article  CAS  PubMed  Google Scholar 

  • Tilg H, Moschen AR (2010) Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52:1836–1846

    Article  CAS  PubMed  Google Scholar 

  • Tipper JP, Witters LA (1982) In vitro phosphorylation and inactivation of rat liver acetyl-CoA carboxylase purified by avidin affinity chromatography. Biochim Biophys Acta 715:162–169

    Article  CAS  PubMed  Google Scholar 

  • Toussant MJ, Wilson MD, Clarke SD (1981) Coordinate suppression of liver acetyl-CoA carboxylase and fatty acid synthetase by polyunsaturated fat. J Nutr 111:146–153

    CAS  PubMed  Google Scholar 

  • Towle HC (2005) Glucose as a regulator of eukaryotic gene transcription. Trends Endocrinol Metab 16:489–494

    Article  CAS  PubMed  Google Scholar 

  • van der Heijden GJ, Wang ZJ, Chu ZD, Sauer PJ, Haymond MW, Rodriguez LM, Sunehag AL (2010) A 12-week aerobic exercise program reduces hepatic fat accumulation and insulin resistance in obese, Hispanic adolescents. Obesity (Silver Spring) 18:384–390

    Article  Google Scholar 

  • Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34:274–285

    Article  CAS  PubMed  Google Scholar 

  • Vos MB, Lavine JE (2013) Dietary fructose in nonalcoholic fatty liver disease. Hepatology 57:2525–2531

    Article  CAS  PubMed  Google Scholar 

  • Wakil SJ (1989) Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 28:4523–4530

    Article  CAS  PubMed  Google Scholar 

  • Wakil SJ, Porter JW, Gibson DM (1957) Studies on the mechanism of fatty acid synthesis. I. Preparation and purification of an enzymes system for reconstruction of fatty acid synthesis. Biochim Biophys Acta 24:453–461

    Article  CAS  PubMed  Google Scholar 

  • Walker PR, Bailey E (1969) Role of “malic enzyme” in lipogenesis. Biochim Biophys Acta 187:591–593

    Article  CAS  PubMed  Google Scholar 

  • Wattacheril J, Chalasani N (2012) Nonalcoholic fatty liver disease (NAFLD): is it really a serious condition? Hepatology 56:1580–1584

    Article  PubMed  PubMed Central  Google Scholar 

  • Woo SL, Xu H, Li H, Zhao Y, Hu X, Zhao J, Guo X, Guo T, Botchlett R, Qi T, Pei Y, Zheng J, Xu Y, An X, Chen L, Chen L, Li Q, Xiao X, Huo Y, Wu C (2014) Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity. PLoS One 9, e91111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu C, Kang JE, Peng L, Li H, Khan SA, Hillard CJ, Okar DA, Lange AJ (2005) Enhancing hepatic glycolysis reduces obesity: differential effects on lipogenesis depend on site of glycolytic modulation. Cell Metab 2:131–140

    Article  CAS  PubMed  Google Scholar 

  • Yang Z-H, Miyahara H, Hatanaka A (2011) Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-Ay Mice with genetic type 2 diabetes. Lipids Health Dis 10:120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yi X, Cao S, Chang B, Zhao D, Gao H, Wan Y, Shi J, Wei W, Guan Y (2013) Effects of acute exercise and chronic exercise on the liver leptin-AMPK-ACC signaling pathway in rats with type 2 diabetes. J Diabetes Res 2013:946432

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yin HQ, Kim M, Kim JH, Kong G, Kang KS, Kim HL, Yoon BI, Lee MO, Lee BH (2007) Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice. Toxicol Appl Pharmacol 223:225–233

    Article  CAS  PubMed  Google Scholar 

  • You M, Fischer M, Deeg MA, Crabb DW (2002) Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). J Biol Chem 277:29342–29347

    Article  CAS  PubMed  Google Scholar 

  • You M, Matsumoto M, Pacold CM, Cho WK, Crabb DW (2004) The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 127:1798–1808

    Article  CAS  PubMed  Google Scholar 

  • Zakim D (1973) Influence of fructose of hepatic synthesis of lipids. Prog Biochem Pharmacol 8:161–188

    CAS  PubMed  Google Scholar 

  • Zimmet P, Magliano D, Matsuzawa Y, Alberti G, Shaw J (2005) The metabolic syndrome: a global public health problem and a new definition. J Atheroscler Thromb 12:295–300

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA

    Shih-Lung Woo, Ting Guo & Chaodong Wu

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  2. Ting Guo
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    James M. Ntambi

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Woo, SL., Guo, T., Wu, C. (2016). Hepatic Lipogenesis: Nutritional Control and Pathophysiological Relevance. In: Ntambi, J. (eds) Hepatic De Novo Lipogenesis and Regulation of Metabolism. Springer, Cham. https://doi.org/10.1007/978-3-319-25065-6_10

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