Monday, October 01, 2007

The long and the short of fatty liver

Too much fat in the liver predisposes to diabetes, but a study in the October issue of Nature Medicine reports that not all types of fat are equally harmful. Changing the fat composition in the liver may therefore help obese patients who are insulin resistant and cannot lose weight.

Excessive fat intake leads to obesity and overwhelms the storage capacity of fat cells, with surplus fat being stored in the liver. Development of fatty liver can result in insulin resistance and increased glucose levels—two hallmarks of diabetes.

Hitoshi Shimano and his colleagues created a strain of mice lacking Elovl6, an enzyme that increases the length of the carbon chains of fatty acids, thereby changing the fat composition in the liver of these mutant mice, with shorter fatty acids predominating over those with longer chains. On a high-fat diet, these mice became obese and developed fatty liver, just like wild-type mice, but their insulin sensitivity and their sugar levels were not affected.

The absolute levels of fat in the liver do not therefore seem to be detrimental to maintaining normal glucose levels. Instead, the types of fat that are present seem to be a more important factor, with shorter fat molecules being healthier than longer ones. If this is also true in humans, it may be possible to help obese patients who are insulin resistant and cannot lose weight by targeting Elovl6.
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