Despite the high fat content of this diet, the study animals maintained normal levels of circulating lipids, she explains. We wanted to learn what factors might be responsible for creating this state in which consumed calories were being burned off in the liver rather than being stored as fat.

Because the physiologic changes in the animals didnt appear to be explained by typical hormonal regulators neurotransmitters that normally regulate appetite -- the researchers set out to identify which genes were unique to this ketogenic phenotype, exploring the possibility that hepatocytes were playing an active role in the process.

And, using micoarray gene analysis, they discovered that their hunch was correct: FGF21, a liver-derived fibroblast growth factor gene, was significantly increased in the mice that had been fed ketogenic diets.

FGF21 had previously been identified as a potential metabolic regulator by scientists at Eli Lilly, who showed that transgenic mice that overexpressed FGF21 were protected from diet-induced obesity, had smaller fat cells and had more brown adipose tissue,says Maratos-Flier. But little was actually known about FGF21s physiologic roles. Working with Jeffrey Fliers lab, we were able to show that FGF21 is essential for fatty acid oxidation.

Furthermore, she explains, when FGF21 was inhibited, the mice developed a massive accumulation of fat in the liver and an extreme increase in circulating lipids.

A second study by Maratos-Flier and colleagues published in the June 2007 issue of the American Journal of Physiology further elucidates the unique metabolic changes that occur with the consumption of a ketogenic diet.

Although the purpose of both of these studies was to glean insights into metabolic physiology, our findings suggest that increased levels of FGF21 may be a potential mechanism behind low-carbohydrate diet
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
5-Jun-2007