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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
15
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
UNC Nutrition Research Institute
Kannapolis, North Carolina, United States
Mean Change in Liver Fat Content Based on Elastography
Elastography (Fibroscan) will be used to measure changes in liver fat.
Time frame: between week 0 (Baseline) and week 3
Mean Percent Change in Liver Fat Content Based on MRI
Magnetic resonance imaging (MRI) will be used to measure changes in liver fat (% change in fat fraction).
Time frame: between week 0 (Baseline) and week 3
Mean Change in Serum Concentrations of Very Low Density Lipoprotein-triglycerides (VLDL-TG)
VLDL-TG measurement in serum (mg/dl) at week 0 and Week 3.
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum Very Low Density Lipoprotein-triglycerides (VLDL-TG)
Area under curve (AUC) (mg\*hr/dl) of serum VLDL-TG for baseline and 3hr time points at week 0 and Week 3.
Time frame: between week 0 (Baseline) and week 3
Mean Change in Serum Concentrations of Triglycerides
Fasting concentrations of serum triglycerides (mg/dl) will be measured at week 0 and 3
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum Triglycerides
Area under curve (AUC) (mg\*hr/dl) of serum VLDL-TG for baseline and 3hr time points at week 0 and Week 3.
Time frame: between week 0 (Baseline) and week 3
Mean Change in Serum Concentrations of HDL Cholesterol
Fasting concentrations of serum HDL cholesterol (mg/dl) will be measured at week 0 and week 3.
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum HDL Cholesterol
Area under curve (AUC) (mg\*hr/dl) of serum HDL cholesterol for baseline and 3hr time points at week 0 and Week 3.
Time frame: between week 0 (baseline) and week 3
Mean Change in Serum Concentrations of LDL Cholesterol
Fasting concentrations of serum LDL cholesterol (mg/dl) will be measured.at week 0 and week 3
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum LDL Cholesterol
Area under curve (AUC) (mg\*hr/dl) of serum LDL cholesterol for baseline and 3hr time points at week 0 and Week 3.
Time frame: Week 0 (baseline) and week 3
Mean Change in Serum Concentrations of Total Cholesterol
Fasting serum concentrations of total cholesterol (mg/dl) will be measured at week 0 and week 3
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum Total Cholesterol
Area under curve (AUC) (mg\*hr/dl) of serum total cholesterol for baseline and 3hr time points at week 0 and Week 3.
Time frame: week 0 and week 3
Mean Changes in Serum Concentrations of Uric Acid
Fasting concentrations of serum uric acid (ng/ml) will be measured at week 0 and week 3
Time frame: between week 0 (Baseline) and week 3
Mean Changes in AUC of Serum Uric Acid
Area under curve (AUC) (ng\*hr/ml) of serum uric acid for baseline and 3hr time points at week 0 and Week 3.
Time frame: between week 0 (Baseline) and week 3
Mean Change in Serum Concentrations of Liver Function Marker (Alanine Transaminase- ALT).
Fasting concentrations of serum ALT (nmol) will be measured at week 0 and week 3
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum Alanine Transaminase (ALT)
Area under curve (AUC) (nmol/hr) of serum ALT for baseline and 3hr time points at week 0 and Week 3.
Time frame: between week 0 (Baseline) and week 3
Mean Change in Serum Concentrations of Liver Function Marker (Aspartate Transaminase-AST).
Serum concentrations of serum AST will be measured at week 0 and week 3
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum Aspartate Transaminase (AST).
Area under curve (AUC) (IU\*hr/L) of serum AST for baseline and 3hr time points at week 0 and Week 3.
Time frame: between week 0 (Baseline) and week 3
Mean Change in Serum Concentrations of Liver Function Marker (Alkaline Phosphatase-ALP)
Fasting concentrations of serum ALP (nmol) will be measured at week 0 and week3
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum Alkaline Phosphatase (ALP)
Area under curve (AUC) (nmol/hr) of serum ALP for baseline and 3hr time points at week 0 and Week 3.
Time frame: between week 0 (Baseline) and week 3
Mean Change in Serum Concentrations of Liver Function Marker (Gamma Glutamyl Transpeptidase-GGT)
Serum concentrations of GGT will be measured at week 0 and week 3
Time frame: between week 0 (Baseline) and week 3
Mean Change in AUC of Serum Gamma Glutamyl Transpeptidase (GGT)
Area under curve (AUC) (IU\*hr/dl) of serum VLDL-TG for baseline and 3hr time points at week 0 and Week 3.
Time frame: between week 0 (Baseline) and week 3
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