The scientists used an established system, based on a recombinant adenovirus, to import the gene responsible for production of elongase-5 into the livers of obese, diabetic mice. When this "delivery system" began to function and the mice produced higher levels of the enzyme, their diet-induced liver defects and elevated blood sugar disappeared.
"The use of a genetic delivery system such as this was functional, but it may not be a permanent solution," Jump said. "For human therapy, it would be better to find a drug that could accomplish the same thing, and that may be possible. There are already drugs on the market, such as some fibrate drugs, that induce higher levels of elongase-5 to some extent."
There are also drugs used with diabetic patients that can lower blood sugar levels, Jump said, but some have side effects and undesired complications. The potential for raising levels of elongase-5 would be a new, specific and targeted approach to diabetes therapy, he said. While lowering blood sugar, the elevated levels of elongase-5 also reduced triglycerides in the liver, another desirable goal. Elevated triglycerides are associated with "fatty liver," also known as non-alcoholic fatty liver disease. This can progress to more severe liver diseases such as fibrosis, cirrhosis and cancer.
Further research is needed to define the exact biological mechanisms at work in this process, and determine what the fatty acids do that affects carbohydrate and triglyceride metabolism, he said. It appears that high fat diets suppress elongase-5 activity.
"These studies establish a link between fatty acid elongation and hepatic glucose and triglyceride metabolism," the researchers wrote in their report, "and suggest a role for regulators of elongase-5 activity in the treatment of diet-induced hyperglycemia and fatty liver."
|Contact: Donald Jump|
Oregon State University