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Study identifies new regulator of fat metabolism

BOSTON -- Over the past several years, animal studies have shown that high-fat, low-carbohydrate ketogenic diets cause demonstrable changes in metabolism and subsequent weight loss. Now, researchers at Beth Israel Deaconess Medical Center (BIDMC) have identified a key mechanism behind this turn of events. Their findings, which appear in the June 2007 issue of Cell Metabolism, demonstrate that a liver hormone known as FGF21 is required to oxidize fatty acids and thereby burn calories.

"When the diet is extremely low in starches and sugars, blood sugar levels drop substantially so that muscle and brain have to turn to alternative fuels, explains senior author Eleftheria Maratos-Flier, MD, an investigator in the Department of Endocrinology, Diabetes and Metabolism at BIDMC and Associate Professor of Medicine at Harvard Medical School. Consequently, fatty acids are broken down in the liver and converted to ketones, which then serve as a major fuel source.

Known as ketosis, this metabolic state is characterized by extremely low insulin levels, as would occur during periods of fasting or starvation or while consuming a low-carb diet, such as the popular Atkins diet model.

For the past several years, Maratos-Fliers laboratory has been studying the physiologic states of animals consuming various types of diets -- including standard animal chow diets and diets moderately high in both fats and carbohydrates, as well as ketogenic diets. And she has found through her experiments that even though mice are fed exactly the same number of calories, the composition of the calories causes them to gain weight in different ways.

The differences in weight gain reflect differences in metabolic rates, she explains. These, in turn, result in hormonal changes that lead to different disposition of the calories.

In this latest paper, Maratos-Flier and colleagues studied mice that had been fed a ketogenic diet high in both saturated fat an
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
5-Jun-2007


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