NAFLD is regarded unquestionably as one of the components of the metabolic syndrome. Hence, metabolic perturbations occurring in the fatty liver become a systemic metabolic derangement. The

phenotypic switching from fatty liver to NASH entails a reprogramming of liver metabolism to fit a stressful metabolic environment. Access through your institution Buy or subscribe This is a

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et al_. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. _PLoS Genet._ 7, e1001324

(2011). Article  CAS  Google Scholar  * Newgard, C.B. _ et al_. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin

resistance. _Cell Metab._ 9, 311–326 (2009). Article  CAS  Google Scholar  * Wang, T.J. _ et al_. Metabolite profiles and the risk of developing diabetes. _Nat. Med._ 17, 448–453 (2011).

Article  Google Scholar  * Shah, S.H. _ et al_. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. _Circ.

Cardiovasc. Genet._ 3, 207–214 (2010). Article  CAS  Google Scholar  * Sookoian, S. _ et al_. Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver

methylation of the peroxisome proliferator-activated receptor gamma coactivator 1α promoter. _Hepatology_ 52, 1992–2000 (2010). Article  CAS  Google Scholar  * Pirola, C.J. _ et al_.

Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease. _Gut_ 62, 1356–1363 (2013). Article  CAS  Google Scholar  *

Sanyal, A.J. _ et al_. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. _Gastroenterology_ 120, 1183–1192 (2001). Article  CAS  Google Scholar

  * Sookoian, S. & Pirola, C.J. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological

severity of nonalcoholic fatty liver disease. _Hepatology_ 53, 1883–1894 (2011). Article  CAS  Google Scholar  * Anstee, Q.M. & Day, C. P. The genetics of NAFLD. _Nat. Rev.

Gastroenterol. Hepatol._ 10, 645–655 (2013). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS The authors are partially supported by grants PICT 2010-0441 and PICT 2012-159

(Agencia Nacional de Promoción Científica y Tecnológica), and UBACYT CM04 (Universidad de Buenos Aires). S.S. and C.J.P. belong to Consejo Nacional de Investigaciones Científicas (CONICET).

AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires–National Scientific

and Technical Research Council (CONICET), Combatiente de Malvinas 3150, Ciudad Autónoma de Buenos Aires 1427, Argentina Silvia Sookoian * Department of Molecular Genetics and Biology of

Complex Diseases, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires–National Scientific and Technical Research Council (CONICET), Combatiente de Malvinas 3150, Ciudad

Autónoma de Buenos Aires 1427, Argentina Carlos J. Pirola Authors * Silvia Sookoian View author publications You can also search for this author inPubMed Google Scholar * Carlos J. Pirola

View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Silvia Sookoian. ETHICS DECLARATIONS COMPETING INTERESTS The

authors declare no competing financial interests. POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sookoian,

S., Pirola, C. Metabolic make-up of NASH: from fat and sugar to amino acids. _Nat Rev Gastroenterol Hepatol_ 11, 205–207 (2014). https://doi.org/10.1038/nrgastro.2014.25 Download citation *

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