Serum metabolites linked to NAFLD may be heritable, research shows

Serum metabolites associated with nonalcoholic fatty liver disease may be heritable, according to research presented this week at The Liver Meeting® - held by the American Association for the Study of Liver Diseases.

Nonalcoholic fatty liver disease, commonly called NAFLD, is a group of liver diseases characterized by an excessive accumulation of fat in the liver, usually occurring in patients who consume little to no alcohol. It is the most common chronic liver disease in children and adults, affecting 80 to 100 million people worldwide.

Studies have shown that NAFLD is heritable and has a shared genetic risk factor for metabolic syndrome, which is a group of medical conditions (e.g., high blood pressure, high blood sugar, high cholesterol) that can lead to serious diseases and conditions, such as heart disease and diabetes. Serum metabolite is the small molecule intermediate product of a metabolic reaction that can be detected in serum extracted from coagulated blood. By studying serum metabolites, investigators can identify which metabolic reactions or pathways have been altered in a disease. While several serum metabolites are known to be associated with NAFLD, they have not been assessed for heritability.

To address this, researchers led by Rohit Loomba, MD, director of the NAFLD Research Center at the University of California, San Diego conducted a study to investigate whether heritability exists in serum metabolites associated with NAFLD and if there are any shared genetic effects. Cyrielle Caussy, MD, PhD, an endocrinologist from Lyon 1 University and a visiting scholar at the NAFLD Research Center, will be presenting these novel findings on behalf of the team of investigators.

"If a serum metabolite is heritable and has a shared gene effect with NAFLD, then it could be a useful biomarker of the disease and could potentially be targeted to improve NAFLD in the future," says Dr. Caussy.

The researchers analyzed a group of 156 people all living in Southern California. The cohort was made up of 37 identical twins, 13 fraternal twins, and 28 sets of sibling/sibling and parent/offspring pairs. Using advanced MRI techniques, the researchers assessed each participant for fat and fibrosis content in the liver. Next, serum metabolites were assessed. And, finally the team looked at the influence of genes and environment to estimate the heritability of the serum metabolites and the shared gene effect between serum metabolites and NAFLD.

Among the group of 156, 36 people with NAFLD were identified. Of 713 serum metabolites analyzed, 440 were found to be heritable. Among them, 56 serum metabolites had a shared gene effect with NAFLD when the researchers adjusted their findings to consider age, sex, and Hispanic ethnicity.

"We found that the novel serum metabolite, phenyllactate (derived from gut‐biome), had a significant shared gene effect with NAFLD," explains Dr. Caussy of the findings. "This suggests a potential link between genetics and gut‐microbiome in the development of NAFLD and provides evidence that several serum metabolites associated with NAFLD are heritable."

These findings may be useful biomarkers of disease severity and could also potentially be targeted to improve treatment for NAFLD.

"Our next goal is to validate these findings across the entire spectrum of NAFLD, and assess if phenyllactate decreases with the improvement of NAFLD treatments," says Dr. Loomba.