The benefits sometimes seen in those on a low-carbohydrate, high-fat diet may depend on increased levels of a newly identified "starvation hormone" produced by the liver, according to a report in the June issue of the journal Cell Metabolism, published by Cell Press. Two studies in the issue show that the hormone plays a critical role in the metabolic shift seen in animals after a period of fasting and in those fed an Atkins-like diet. That shift is characterized by an increased reliance on fat stores as an alternative source of fuel when glucose, the bodys primary energy source, plummets.

A team led by Eleftheria Maratos-Flier of Harvard University reports evidence that increased blood levels of liver-derived "fibroblast growth factor 21" (FGF21) are required for fasted mice and mice on a carbohydrate-restricted diet to switch gears and begin burning fat. Likewise, an accompanying study led by Steven Kliewer of the University of Texas Southwestern Medical Center found that FGF21 mobilizes fat in food-restricted animals and those with chronically elevated concentrations of the liver hormone. Kliewers team further showed that the hormone contributes to energy-conserving behavioral changes as animals ride out food shortages.

"Whats really exciting is that mice with excess FGF21even when they are fedlook like they are fasted," Kliewer said. "Its startling that you can give one hormone and flip the whole metabolic profile."

"We think these findings would increase the desirability of a drug that [might work through this mechanism] to increase fat oxidation in the liver," added Maratos-Flier, noting that the rise in obesity has contributed to a growing epidemic of nonalcoholic fatty liver disease. Although the physiology remained uncertain, pharmacological studies of mice and diabetic monkeys had previously shown promise for FGF21 therapy as a means to lower blood sugar and lipids and stave off weight gain.

Mammals survive period
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Contact: Erin Doonan
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617-397-2802
Cell Press
5-Jun-2007