Goran Lab: Nutrigenetic Intervention to Reduce Liver Fat in Hispanics

Spoonful of sugar

The prevalence of pediatric non-alcoholic fatty liver disease (NAFLD) has doubled in the last 20 years and prevalence is most severe among Latinos. NAFLD is now the most common form of liver disease and over time can lead to cirrhosis and eventually liver cancer.

Potential role of nutrigenetics

Nutrigenetics—the effect of genetic variation on dietary response—may help explain the higher prevalence of NAFLD among Latinos. In part, a genetic predisposition causes this increased susceptibility to high liver fat. Fifty percent of the Latino population have a particular variant in their DNA sequence (a polymorphism), called the PNPLA3 gene that is a major contributor to explain the higher incidence of NAFLD. Our previous studies, as well as recent studies in animal models, provide compelling evidence that high dietary sugar exacerbates the impact of the PNPLA3 variant on liver fat.

Current approaches to reducing liver fat, however, involve general advice on weight loss and healthy eating. They do not directly address the mechanism of excess fat accumulation in the liver, especially as it relates to this genetic predisposition in Latinos.

Study design

With this study, we aim to develop innovative strategies with the potential for long-term sustainability. These strategies will address elevated liver fat in obese Latino children and adolescents based on genetic predisposition. This randomized, nutrigenetic clinical trial of dietary sugar reduction in children diagnosed with NAFLD examines whether differential treatment responses based on the PNPLA3 genotype exist.

We will recruit 180 overweight and obese Hispanic children (12-18 years old) with clinically verified NAFLD and randomize them to one of two 16-week interventions:

  1. Standard of care for healthy eating (control/placebo group)
  2. Reduction of dietary sugars to 10% of total calories (treatment group)

Outcome measures

We will measure the following metrics before and after intervention:

  • Total liver fat, liver scarring and deep and superficial abdominal fat tissue volume using 3T MRI
  • Total body fat by DEXA
  • Plasma liver enzymes, fasting insulin, glucose, lipids, free fatty acids and inflammatory markers using blood tests
  • Insulin and glucose response to an oral glucose challenge test

Study hypothesis

We hypothesize that:

  1. Liver fat content and metabolic outcomes, such as lipids and inflammatory biomarkers, will show significantly greater improvements with sugar reduction relative to control.
  2. The success of the treatment will depend on the participant’s genotype. Participants without the PNPLA3 gene variant will show a more significant reduction in liver fat compared to those with the variant.

These results will provide efficacy data for a novel treatment strategy to reduce liver fat in obese Hispanic children and adolescents with NAFLD. Furthermore, this study has the potential to impact personalized dietary recommendations for treatment and prevention of NAFLD in Hispanics as a function of genetic predisposition.

ClinicalTrials.gov Identifier: NCT0294864