Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications

Authors

  • Elisa Fabbrini,

    1. Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
    2. Center for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele, Rome, Italy
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  • Shelby Sullivan,

    1. Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
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  • Samuel Klein

    Corresponding author
    1. Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
    • Center for Human Nutrition, Washington University School of Medicine, 660 S. Euclid Avenue, Box 8031, St. Louis, MO 63110-1093===

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    • fax: 314-362-8230.


  • Potential conflict of interest: Dr. Klein owns stock in Aspiration Medical Technologies. He advises and received grants from Ethicon Endosurgery.

Abstract

Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Steatosis, the hallmark feature of NAFLD, occurs when the rate of hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and export (as triglyceride within very low-density lipoprotein). Therefore, an excessive amount of intrahepatic triglyceride (IHTG) represents an imbalance between complex interactions of metabolic events. The presence of steatosis is associated with a constellation of adverse alterations in glucose, fatty acid, and lipoprotein metabolism. It is likely that abnormalities in fatty acid metabolism, in conjunction with adipose tissue, hepatic, and systemic inflammation, are key factors involved in the development of insulin resistance, dyslipidemia, and other cardiometabolic risk factors associated with NAFLD. However, it is not clear whether NAFLD causes metabolic dysfunction or whether metabolic dysfunction is responsible for IHTG accumulation, or possibly both. Understanding the precise factors involved in the pathogenesis and pathophysiology of NAFLD will provide important insights into the mechanisms responsible for the cardiometabolic complications of obesity. (HEPATOLOGY 2009.)

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