~ In With The New, Out With The Old: It Takes New Fat to Burn Existing Fat

The May 2005 issue of Cell Metabolism (http://www.cellmetabolism.org/) published an article concerning the discovery by Clay F Semenkovich, MD and colleagues at Washington University School of Medicine in St Louis that it takes new fat, either obtained from the diet or made in the liver from glucose, to burn the body's pre-existing fat deposits.

Dr Semenkovich's team made their discovery by genetically engineering mice to lack a fat-synthesizing enzyme in the liver, rendering them unable to manufacture new fatty acids. When the animals, which are called FASKOL (Fatty Acid Synthase KnockOut in Liver) mice, were provided with a diet that contained no fat, they developed fatty liver disease, a condition that can occur in obese humans, and low blood sugar. Both conditions were reversed when the mice were given diets that contained fat or a drug that activates PPAR-alpha, a protein that is needed to extract energy from carbohydrates and fats. Because the drug elicited the same results as adding fat to the diet, the team concluded that new fat may be necessary to initiating the PPAR-alpha pathway.

Dr Semenkovich, who is a professor of medicine and cell biology and physiology, explained the findings: "When we took dietary fat away from the FASKOL mice, their livers quickly filled with fat. Their 'old' fat stores mobilized to the liver, but their livers could not initiate fat burning, and the fat just accumulated. We concluded that to regulate fat burning, the liver needs 'new' fat."

He added, "Scientists have argued that PPAR-alpha is activated by fats. But we've never known which fats or where they come from. This study suggests that new fat is a 'key' that unlocks the 'door' for PPAR-alpha in the liver. There's also good evidence that the liver plays a key role in mediating cardiovascular risk through the secretion of multiple proteins associated with inflammation. In these mice we found that when too much fat got into the liver, there was excessive inflammation."

The team is now investigating which fats can be given to activate the PPAR-alpha pathway. Dr Semenkovich suggests that dieters who want to lose fat stored in peripheral tissues could consume small amounts of fats, such as fish oils, that might activate fat-burning pathways through the liver.

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