This is a study to investigate genetic predisposition to hepatic steatosis and the expression of gluconeogenic and lipogenic genes in livers of obese children and adolescents.

Hypothesis 1: Common variants recently associated with variation in plasma TG levels identified in Genome Wide Association Studies (GWAS) (such as GCKR, PNPLA3) can affect accumulation of fat and subsequent development of Non Alcoholic Fatty Liver Disease (NAFLD). Gene variants act in additive or synergistic manner with progressive liver fat accumulation per additional risk allele.

Hypothesis 2: With increase in hepatic fat content NASH and fibrosis will increase. Furthermore, expression of lipogenic markers (SREBP1c) will increase.

To establish a cohort of obese youths to prospectively analyze potential factors (genetic and nutritional factors) that might affect the expression and progression of NAFLD. This study will determine genetic markers and their ability to convey susceptibility to NAFLD in obese children and adolescents. Furthermore, potential mechanisms that might contribute to the accumulation of hepatic Triglyceride (TG) accumulation will be, for the first time, assessed by genotyping. Additionally, we will examine the presence of intestinal microbiome in the development of fatty liver through stool collection.

Inclusion Criteria:

• between 7 and 18 years of age,
• overweight or obese with a BMI greater than the 85th percentile for age and gender, and
• be otherwise healthy.

Exclusion Criteria:

• the use of any medication that alters liver function, blood pressure, glucose or lipid metabolism and
• no use of any antipsychotic medication
• Youth on chronic anti-inflammatory medications or who consume alcohol are also excluded.

The majority of the research subjects will be recruited from the Yale Pediatric Obesity Clinic and the Endocrine Clinic.