Researchers have discovered a potential target for the development of new therapies to treat hypertriglyceridemia, a lipid disorder commonly seen in obese and diabetic people.
Diabetes researchers in the Division of Immunogenetics at the John G. Rangos Sr. Research Center at Children's Hospital of Pittsburgh of UPMC, focussed their study on the role of a protein known as Forkhead Box O1 (FoxO1) that controls the metabolism of glucose and cholesterol.
While studying in the laboratory, they successfully managed to stop the secretion of triglycerides in animals that were obese and diabetic by inhibiting the production of FoxO1 in the liver.
"Our latest findings suggest that we may eventually be able to develop drug therapies that inhibit FoxO1, which would thereby inhibit the production of proteins that lead to elevated triglyceride levels in people who are obese and/or who suffer from type 2 diabetes. Hypertriglyceridemia is a known risk factor for developing heart disease, the leading cause of death in the United States," said Henry Dong, PhD, a diabetes researcher in the Division of Immunogenetics at Children's and senior author of the study.
Dong, who has led the study has been researching the role of FoxO1 for the last seven years and said that elevated triglyceride levels have been identified as a risk factor for heart disease.
His study indicated that FoxO1 is crucial to the regulation of a protein known as microsomal triglyceride transfer protein (MTP). MTP helps in the production of very low-density lipoproteins (VLDL), which are produced in extreme excess in people with hypertriglyceridemia.
Also, it was found that FoxO1 controls insulin action on the production of MTP in the liver. Increased production of MTP due to the inability of insulin to regulate the activity of FoxO1, led to the overproduction of VLDL and hypertriglyceridemia in mice. Mice that were made to be deficient in FoxO1 in the liver experienced reduced MTP and VLDL production.
After determining the role of FoxO1's in the liver, the researchers are now studying its function in other tissues and organs for finding out the impact of such therapies on children and adults who are obese and/or have type 2 diabetes, which put a person at risk for heart disease.
The results of their study are published in upcoming issue of the Journal of Clinical Investigation.