Early-onset obesity in father linked to increased potential for liver disease in child

A history of early-onset paternal obesity increases the odds of elevated liver enzyme levels in offspring and points to the potential for a genetic link between obesity and liver disease, according to a study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.

This new study found that participants with paternal early-onset obesity had higher serum alanine aminotransferase (ALT) levels than those without paternal obesity. These results showed that children with fathers who were defined as clinically obese at an early age were more likely to have increased liver enzyme levels, an indicator of liver disease. A secondary analysis, excluding obese offspring, produced a strengthened connection between paternal early-onset obesity and elevated serum ALT levels, demonstrating that the link between obesity in the father and elevated serum ALT levels in the offspring is independent of the child’s body mass index (BMI) and persists among non-obese children. No relationship between maternal early-onset obesity and ALT levels was found.

Serum ALT levels are a marker of liver disease in the general population. Previous studies have shown that obesity is an important correlate of elevated serum ALT levels, and according to the National Health and Nutrition Examination Survey (NHANES), up to 7 percent of the adult U.S. population has unexplained elevated serum ALT levels. These elevated levels are potentially due to nonalcoholic fatty liver disease (NAFLD), which is now considered to be the most common cause of serum ALT elevations in the U.S. population and is associated with obesity. Elevated serum ALT levels and NAFLD can lead to inflammation of the liver (hepatitis), scarring of the liver (cirrhosis) and liver cancer, a potentially deadly condition.

“Serum ALT elevations and NAFLD are more prevalent than ever in the U.S., though we don’t know specifically what’s causing the increase. Our results point to a genetic connection between early-onset paternal obesity and increased ALT levels,” said Caroline S. Fox, MD, MPH, the senior author of the study and medical officer with the Framingham Heart Study, Framingham, MA. “These findings show that familial factors may play a role in elevated serum ALT levels in the general population.” The Framingham Heart Study is a prospective, community-based, family study supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

Dr. Fox and her colleagues from the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) evaluated participants of the NHLBI’s Framingham Heart Study for their research, using a well-characterized, large community-based sample with detailed clinical examination data available. Both parents had to have been participants in the Framingham Heart Study for the child to qualify. Researchers evaluated 1,732 offspring cohort participants, with an average age of 42 years and an even split of male and female patients. Parental obesity was defined as a BMI of 30 or more on at least two occasions during the follow-up of the original cohort. Early-onset parental obesity was defined as the twenty-fifth percentile of the age at the first obesity among the obese fathers and mothers (41 years in men and 45 years in women).