Using a small Randomized Controlled Trial (RCT) study design, PNPLA3 risk allele carriers (CG/GG genotype) with NAFLD, will be assigned 2:1 to a tailored NAFLD-specific weight loss intervention compared to a wait-list control group.

The Mexican-American population accounts for 64.3% of the U.S. Hispanic population and is the fastest growing Hispanic subgroup. Non-alcoholic fatty liver disease (NAFLD) is a chronic disease associated with obesity that is highest in the nation for Mexican-American men. NAFLD consists of a spectrum of conditions, ranging from fatty liver to cirrhosis and liver cancer. Lack of physical activity and sugar-sweetened beverage consumption are risk factors for NAFLD and are highly evident in the Mexican-American male population. Additionally, Mexican-American men are at increased risk of NAFLD and liver cancer if they are carriers of a version of a gene (PNPLA3) found to increase risk and severity of NAFLD. In the absence of prescription medications, weight loss due to changes in diet and physical activity is recommended for the prevention and treatment of NAFLD. Changes in lifestyle that result in >5% body weight loss have been shown to improve levels of liver fat and even reverse the condition. Despite the clear need to develop effective intervention strategies for Mexican-American men, no studies to date have explored the use of health risk assessment strategies, including genetic risk, to motivate behavior change to reduce the risk of NAFLD in Mexican-American men. Consequently, this will be the first weight loss intervention for Mexican-American men to incorporate genetic predisposition and lifestyle risk factors of NAFLD (e.g., dietary sugar consumption), as a strategy to improve engagement in weight loss and weight maintenance behaviors.

Inclusion Criteria:

• Self-identify as a Mexican or Mexican-American man
• 18-64 years of age
• BMI between 30 to 50.0 kg/m²
• Have a CAP score ≥248 at screening
• Be identified as PNPLA3 risk allele carriers (CG/GG genotype) at screening
• Be able to provide informed consent
• Speak, read, and write either English and/or Spanish.

Exclusion Criteria:

• Have active, chronic gastrointestinal disorder (e.g. inflammatory bowel disease, ulcerative colitis, Chron's disease, celiac disease)
• Been previously diagnosed with viral hepatitis, liver disease or liver cancer
• Have a history of bariatric surgery
• Report medical condition or treatment for a medical condition that could affect body weight or ability to engage in structured physical activity that is consistent with the intervention for this study
• Have current congestive heart failure, angina, uncontrolled arrhythmia, or other symptoms indicative of an increased acute risk for a cardiovascular event
• Have a resting systolic blood pressure of ≥150 mmHg or resting diastolic blood pressure of ≥100 mmHg
• Have an eating disorders that would contraindicate weight loss or physical activity
• Report significant alcohol consumption (e.g., drinking ≥ 21 standard drinks/week, binge drinkers, or those with previous heavy alcohol consumption) identified by the Alcohol Use Disorders Identification Test
• Currently treated for psychological issues (e.g., depression, bipolar disorder, etc.), taking psychotropic medications with the previous 12 months, or hospitalized for depression within the previous 5 years
• Report exercise on ≥3 days per week for ≥ 20 minutes per day over the past 3 months
• Report weight loss of ≥5% or participating in a weight reduction diet program in the past 3 months
• Taking any medication or supplement known to affect body composition or history of exposure to hepatotoxic drugs
• Report plans to relocate to a location that limits their access to the study site or having employment, personal, or travel commitments that prohibit attendance to all of the scheduled assessments.

The final dataset will be stripped of identifiers prior to release for sharing. Dr. Garcia will make the data and associated documentation available to users under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed. The final dataset, including all study variables, will be developed for import into standard statistical software programs including SPSS, SASS and STATA.

The final dataset will be cleaned and organized during the final study year and will be available only to the study PI or designees (Co-Investigators, Collaborators) for 36-months post-study completion. At that time the dataset then will be made more widely available through data use agreements with the PI/University of Arizona. Access will require registration including investigator name, credentials, and academic affiliation.

Dr. Garcia will make the data and associated documentation available to users under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed. All study data collection forms will be made available as pdf files; data collection time-points and dictionary of data definitions also will be made available.

Assessments will be performed at 0, 6, and 12-months post-intervention. To minimize the potential for bias, outcome assessors will be blinded to treatment condition.