The study by researchers at the Washington University School of Medicine, shows that fats taken in directly from the diet or generated from sugars spark a cascade of gene activity in the liver necessary for healthy blood levels of sugar, cholesterol, and other fats.

According to the researchers, they found that old fat stores alone failed to set those critical metabolic pathways in motion, and the study in mice suggests that normal metabolism requires so-called "new" fat, evidence which supports the theory that a healthy diet should include an adequate source of fat.

Senior study author Clay Semenkovich, says that "de novo synthesis of fat" is an energy-expensive process whose role in adult mammals is poorly understood, and the current study supports the notion that the source of fats affects their physiology. New fats are required to burn fat normally and to maintain glucose and cholesterol levels within the normal range.

Semenkovich says the findings confirm the importance of a balanced diet for a healthy metabolism and weight loss, and also suggests that specially engineered fats might boost healthy liver metabolism, offering an alternative mechanism for fighting chronic diseases, including obesity, diabetes, and heart disease.

In the study researchers inactivated fatty-acid synthase, an enzyme that generates new fat from carbohydrates, in the livers of mice, and found that when fed a diet completely lacking fat, the mice developed low blood sugar and fatty liver. Both conditions were reversed when the researchers restored fat to the animals' diets.

The paradox says Semenkovich, was that when they inactivated fatty-acid synthase in the liver and eliminated fat in the diet, the animals became sick, with livers full of fat.

Further examination also found that, in the absence of new fat, the mice exhibited a marked decline in the activity of genes critical for the metabolism of glucose, fatty acids, and cholesterol, genes which are normally targeted by PPARa, a key energy management gene activated by fatty acids.

"In short", says Semenkovich "all fatty acids are not created equal, at least not in the liver".

In conclusion, say the researchers, it suggests that products of fatty acid synthesis regulate glucose, lipid, and cholesterol metabolism by activating distinct pools of PPARa in the liver, but further study will be needed to elucidate the mechanism by which nutrient sensors in the body distinguish between different sources of fat.

The study is published in the May issue of Cell Metabolism.

cellpress/