title: Genetic-related and carbohydrate-related factors affecting liver fat accumulation.
abstract: OBJECTIVE
  To summarize recent findings that have examined dietary, genetic and gene-diet interactions that contribute to fat accumulation in the liver during growth and development, with particular focus on contributions relating to dietary carbohydrate and sugar consumption. In addition, this review highlights how some of these contributions to liver fat vary across the population in terms of ethnic-specific effects.
  
  
  RESULTS
  Dietary carbohydrate, and especially sugars contribute to increased liver fat accumulation due to the lipogenic potential of fructose during liver metabolism. In addition, recent genome-wide studies have identified several polymorphisms that contribute to increased liver fat accumulation, with some of these genes relating to dietary carbohydrate and sugar consumption. In particular, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, which is highly prevalent in Hispanics, contributes to excessive liver fat beginning at a young age, especially in the context of high sugar consumption.
  
  
  CONCLUSIONS
  Dietary sugar contributes to liver fat accumulation, with this being explained by de-novo lipogenesis from fructose in the liver. Certain genetic factors, including PNPLA3, glucokinase regulatory protein and APOC3 contribute to increased liver fat accumulation, with these effects being manifested at an early age. Hispanics in particular are at elevated risk for liver fat accumulation because of the higher frequency of genetic variants such as PNPLA3 and glucokinase regulatory protein as well as an interaction between the PNPLA3 and dietary sugar.
authors.affiliation: Department of Preventive Medicine, Childhood Obesity Research Center, Keck School of Medicine, The University of Southern California, Los Angeles, California, USA. goran@usc.edu
authors.forename: Michael I
authors.initials: MI
authors.lastname: Goran
authors.forename: Ryan
authors.initials: R
authors.lastname: Walker
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004032:Diet / Q000208:ethnology; D004040:Dietary Carbohydrates / Q000378:metabolism* / Q000494:pharmacology; D002149:Energy Intake; D005234:Fatty Liver / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism; D006630:Hispanic or Latino; D006801:Humans; D008049:Lipase / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D053305:Apolipoprotein C-III; D002352:Carrier Proteins; D004040:Dietary Carbohydrates; D005632:Fructose; D008049:Lipase; D008565:Membrane Proteins; C080906:glucokinase regulatory protein; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent