Fatty liver disease prevented in mice

Researchers have discovered a way to prevent nonalcoholic fatty liver disease - the most common cause of chronic liver disease worldwide - in mice.

According to investigators at Washington University School of Medicine in St. Louis, blocking a path that delivers dietary fructose to the liver prevented mice from developing the condition.

First author Brian J. DeBosch, MD, PhD, clinical fellow in pediatric gastroenterology, said that there are competing hypotheses about the origins of metabolic syndrome and one of these hypotheses is that insulin resistance begins to develop in the liver first.

The research team, led by Kelle H. Moley, MD, the James P. Crane Professor of Obstetrics and Gynecology, showed that a molecule called GLUT8 carries large amounts of fructose into liver cells.

In this study, researchers showed that blocking or eliminating GLUT8 in mice reduced the amount of fructose entering the organ and appeared to prevent the development of fatty livers. Mice with GLUT8 deficiency also appeared to burn liver fat at a faster rate than control mice.

The researchers also saw differences between male and female mice in the degree to which they were protected from fatty livers and in whole-body metabolism. Male mice fed a high-fructose diet while deficient in GLUT8 still had evidence of fatty liver disease, but whole-body metabolism was healthy.

They showed no evidence of metabolic syndrome in the rest of the body. Females fed fructose while lacking GLUT8, in contrast, had healthy looking livers but exhibited more evidence of whole-body metabolic syndrome.

The study has been published in The Journal of Biological Chemistry.