Scientists from Wageningen University in the Netherlands have discovered that a factor released from body fat, which they call Fasting-Induced Adipose Factor or FIAF, has a major impact on blood levels of HDL and triglycerides in mice. The factor might be a promising drug candidate, team leader dr. Sander Kersten says. “Our study demonstrates that small changes in the production of FIAF in mice elevate blood HDL and triglycerides.”
Obesity is known to negatively influence the level of cholesterol and other fats in our blood, often causing a condition called dyslipidemia. For many years, researchers have suspected that factors secreted from body fat affect blood lipids, yet promising candidates are hard to find. Kersten explains: “We know that elevated blood levels of HDL are protective against cardiovascular disease, whereas elevated triglycerides are considered harmful. Obese people often have low HDL levels and elevated levels of triglycerides, and are therefore at increased risk for cardiovascular disease.”
“For years we have known that diet has an influence on blood lipids but improvements achieved by dietary changes alone are often unsatisfactory. While statins are very effective in reducing blood LDL levels, they hardly touch HDL and triglycerides. Therefore, there is a need for drugs that specifically address HDL and/or triglycerides. A promising drug candidate may be FIAF.” says Kersten.
The paper, which was published online on November 4 in the Journal of Biological Chemistry, shows that transgenic mice that produce more FIAF have elevated blood HDL and triglyceride levels. According to the paper, FIAF raises triglyceride levels by blocking the removal of triglycerides from blood.
What is remarkable is that FIAF binds to HDL and LDL particles. Many proteins are attached to lipoproteins circulating in blood but almost all of them are produced in liver. It is very unusual to find a protein produced in fat tissue being bound to lipoproteins.
According to Kersten, the binding to lipoproteins also shows a clear difference between mouse and human. “In mice FIAF appears to be bound to both LDL and HDL, but in humans it is only bound to HDL. It is not clear what the implications are of this variation but FIAF might very well act differently in humans than in mice.”
One possibility is that in humans FIAF mainly affects HDL levels and hardly influences triglycerides. Such an effect would be protective against cardiovascular disease.
Whether FIAF is effective towards HDL or triglycerides in humans will ultimately determine its potential as a drug target. “Right now, it is too early to tell. Hopefully, in the next few years we will get better insight into what FIAF actually does in humans”, says Kersten.
Note for the editors
More details can be found in the original paper by Mandard and colleagues, published at JBC online (http://www.jbc.org/cgi/content/abstract/M506519200v1). The work was funded by the Netherlands Organization for Scientific Research, NWO. For more information contact dr. Sander Kersten (Wageningen University, Division of Human Nutrition), tel. + 31 317 485787, e-mail sander.kersten@wur.nl.