Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects one-third of adults and an increasing number of children in developed countries. The disease begins with the aberrant accumulation of triglyceride in the liver, which in some individuals elicits an inflammatory response that can progress to cirrhosis and liver cancer. Although NAFLD is strongly associated with obesity and insulin resistance, its pathogenesis remains poorly understood, and therapeutic options are limited. Here, we discuss recent mechanistic insights into NAFLD, focusing primarily on those that have emerged from human genetic and metabolic studies.

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Volume 332 | Issue 6037
24 June 2011

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Published in print: 24 June 2011


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Acknowledgments: We thank T. Rodgers for the histological sections in Fig. 1 and D. Russell, J. Goldstein, M. Brown, and J. Browning for helpful discussions. The University of Texas Southwestern Medical Center has applied to patent the association between rs738409 and NAFLD. Supported by grants from the NIH (RL1HL092550, UL1DE109584, and PO1 HL20948). H.H.H. is on the Scientific Advisory Board for Pfizer. J.D.H. is a consultant for Merck, Pfizer, and Sanofi-Aventis and is on the Scientific Advisory Board of Aegerion.



Jonathan C. Cohen
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390–9046, USA.
Jay D. Horton
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390–9046, USA.
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390–9046, USA.
Helen H. Hobbs* [email protected]
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390–9046, USA.
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390–9046, USA.
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390–9046, USA.


To whom correspondence should be addressed. E-mail: [email protected]

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