Nutrigenetic Intervention to Reduce Liver Fat in Hispanics

减少西班牙裔肝脏脂肪的营养遗传干预

• 批准号: 9010742
• 负责人: Hooman Allayee
• 金额: $ 78.09万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-24 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9010742
• 关键词: Abdomen; Address; Adipose tissue; Adolescent; Adult; Animal Model; Beverages; Biological Markers; Biological Process; Body Weight decreased; Body fat; Calories; Child; Childhood; Cirrhosis; Clinical Research; Clinical Trials; Control Groups; Data; Data Analyses; Deposition; Diagnosis; Diet; Dietary Intervention; Dietary Sugars; Dual-Energy X-Ray Absorptiometry; Ensure; Enzymes; Equilibrium; Ethical Issues; Ethnic group; Fasting; Fatty acid glycerol esters; Frequencies; Genes; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Glucose; Goals; Guidelines; Healthy Eating; Hispanics; Individual; Inflammatory; Insulin; Intervention; Lead; Lipids; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Malignant neoplasm of liver; Measures; Metabolic; Mus; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Obesity; Oral; Outcome; Overweight; Phospholipase; Placebo Control; Plasma; Populations at Risk; Predisposition; Prevalence; Prevention; Public Health; Publishing; Randomized; Recommendation; Recruitment Activity; Regulation; Reporting; Research Design; Risk; Scheme; Treatment Efficacy; Variant; Visceral; Weight; base; efficacy testing; genome wide association study; group intervention; imaging modality; improved; inflammatory marker; innovation; intervention effect; mouse model; non-alcoholic fatty liver; novel; nutrition related genetics; obesity in children; primary outcome; public health relevance; randomized trial; response; standard of care; subcutaneous; sugar; treatment group; treatment strategy; weight maintenance

 DESCRIPTION (provided by applicant): Almost 40% of obese Hispanic children and adolescents are estimated to have non-alcoholic fatty liver disease (NAFLD). Very few studies have examined the efficacy of treatment strategies for reducing elevated liver fat (ELF), with no studies in Hispanic children and adolescents. Consequently, there are no specific guidelines for treating pediatric NAFLD or reducing ELF other than general advice for weight loss. In addition, a recent genome-wide association study in adults identified a variant in the PNPLA3 gene as a novel factor explaining increased liver fat in Hispanics, but there are no studies that have evaluated the efficacy of treatments for ELF as a function of PNPLA3 genotype. In preliminary data, we show that obese Hispanic children and adolescents who carry the GG genotype of PNPLA3: a) have > 2-fold higher liver fat compared to CC and CG individuals; and b) are more susceptible to liver fat accumulation in the context of high dietary sugar. This latter finding fit with a recently published study in mice and our current, though limited, understanding of the function and regulation of PNPLA3. Taken together, these observations suggest that different dietary strategies may have differential effects on reducing liver fat, depending on PNPLA3 genotype. Therefore, our overall objective is to identify novel interventions that target the mechanism of fat deposition in liver rather than rely on weight loss, which is typically difficult o achieve and challenging to sustain. We therefore propose to conduct a randomized trial to test the efficacy of dietary sugar reduction for improving liver fat content in obese Hispanic children and adolescents and examine whether the effects of this approach vary by PNPLA3 genotype. We will recruit 120 Hispanics (10-18 years) with clinically diagnosed NAFLD and randomize them to 16-week interventions under weight stable conditions: 1) standard of care advice for healthy eating (control/placebo group); and 2) reduction of dietary sugars (treatment group). The following will be measured before and after intervention: total liver fat, liver fibrosis, visceraland subcutaneous abdominal adipose tissue volume by magnetic resonance imaging methods at 3 Tesla; total body fat by DEXA; plasma liver enzymes, fasting insulin, glucose, lipids, free fatty acids, and inflammatory markers, and insulin and glucose response to an oral glucose challenge. The hypotheses are: a) liver fat content and metabolic outcomes, such as lipids and inflammatory biomarkers, will show significantly greater improvements with sugar reduction relative to control; and b) greater benefits in liver fat reduction and metabolic outcomes will be observed in GG subjects relative to CC/CG individuals. These results will provide efficacy data for a novel treatment strategy for ELF in obese Hispanic children and adolescents and has the potential to impact personalized dietary recommendations for treatment and prevention of NAFLD in Hispanics, as a function of genetic predisposition.