Genetic-specific Effects of Fructose on Liver Lipogenesis
Condition: NAFLD
Study type: Interventional

Summary: 
      The primary goal of this study is to identify a set of genotypes that increase the risk for
      nonalcoholic fatty liver disease (NAFLD) and predispose individuals to increased de novo
      lipogenesis (DNL) and liver fat accumulation when exposed to fructose intake. The proposed
      goal will be achieved through the completion of following aims:

        1. To determine the impact of prolonged exposure of fructose on hepatic lipid accumulation
           in Caucasian individuals with high and low genetic risk for NAFLD,

        2. to determine the impact of acute exposure of fructose on hepatic DNL, and

        3. to determine the relationship between markers of DNL, liver fat accumulation and serum
           concentrations of lipids, uric acid and liver function markers before and after the
           fructose challenge.
    

Detailed description: 
      BACKGROUND AND RATIONALE Non-alcoholic fatty liver disease (NAFLD) is characterized by fat
      accumulation in liver cells not caused by alcohol. A leading cause of chronic liver disease
      in the US, NAFLD represents a group of disorders including steatosis, nonalcoholic
      steatohepatitis with fibrosis. It has substantially risen in prevalence over the last two
      decades with the estimated prevalence being 20% among US adults and 25% in young adults
      (18-39 years). Over 64 million individuals are believed to have NAFLD with annual medical
      costs rising to more $100 billion. More common in individuals who are obese or diabetic
      and/or have metabolic syndrome, NAFLD has been associated with increased cirrhosis,
      liver-related mortality and hepatocellular carcinoma.

      Both genetic and environmental, including nutritional, factors contribute to the onset and
      progression of NAFLD. Increased consumption of sugar-sweetened, fructose-rich beverages has
      been linked to NAFLD. Fructose, commonly found in soft drinks, fruit juices and energy
      drinks, affects many metabolic processes, foremost being an increase in fat accumulation in
      the liver and hence, NAFLD. Genome-wide and candidate gene studies have identified several
      genes associated with NAFLD. However, none of these studies have shown the cumulative effects
      of single nucleotide polymorphisms (SNPs) on changes in liver fat when exposed to fructose.
      The results from this study can be extrapolated to larger cohorts and other ethnicities and
      are therefore, expected to lay the foundation for developing personalized nutritional plans.
    

Intervention name(s): Sugar drink
Intervention type(s): Other
Intervention description(s): A sugar drink made with 1.2 g/kg body weight of added sugar( 0.75g/kg body weight of fructose + 0.45g/kg body weight of glucose) and 24oz water
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants are assigned to high genetic risk score group in parallel to low genetic risk score group
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Glucose; Fructose; Fatty-liver; Polymorphisms; Imaging; Fibroscan