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Genetic-related and carbohydrate-related factors affecting liver fat accumulation

Goran, Michael I.; Walker, Ryan; Allayee, Hooman

Current Opinion in Clinical Nutrition & Metabolic Care: July 2012 - Volume 15 - Issue 4 - p 392–396
doi: 10.1097/MCO.0b013e3283544477
CARBOHYDRATES: Edited by Luc Tappy and Bettina Mittendorfer

Purpose of review 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.

Recent findings 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.

Summary 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.

Department of Preventive Medicine, Childhood Obesity Research Center, Keck School of Medicine, The University of Southern California, Los Angeles, California, USA

Correspondence to Michael I. Goran, USC Childhood Obesity Research Center, 2250 Alcazar Street, CSC 200, Los Angeles, CA 90033, USA.Tel: +1 323 442 3027; e-mail:

© 2012 Lippincott Williams & Wilkins, Inc.