Earlier studies also showed that feeding rodents a high-fat, low-carbohydrate ("ketogenic") diet induces lipid oxidation associated with weight loss, according to Maratos-Flier. Yet the underlying mechanism responsible for the profound physiological changes that the diets induced wasnt fully understood.
In the new study, Maratos-Fliers team examined changes in gene activity occurring in mice fed a high-fat, low-carb diet for 30 days. Their comprehensive genetic screen of the animals, which lost weight on the special diet, turned up FGF21.
"We saw a dramatic increase in FGF21 in the livers of the mice [on the diet]," she said. "We thought, Maybe there is something to this."
Through further experimentation, the researchers found that liver and circulating levels of FGF21 increase in mice in response to both a low-carb, high-fat diet and fasting. Moreover, the hormone declined rapidly when fasted animals were fed again. In mice unable to produce FGF21 in their livers, the special diet resulted only in fatty liver, high blood lipids, and reduced blood ketones, due at least in part to altered expression of key genes governing lipid and ketone metabolism.
Meanwhile, Kliewers group identified the FGF21 endocrine hormone as a mediator of peroxisome proliferator-activated receptor " (PPAR"). Scientists have known that PPAR""controls fats use as an energy source during starvation. In addition, some drugs that lower "bad" cholesterol work by targeting PPAR""
Kliewers group showed that FGF21 is induced directly by PPAR" in liver in response t
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Contact: Erin Doonan
edoonan@cell.com
617-397-2802
Cell Press
5-Jun-2007