Low Carb Hormone Discovered in Mice

The low carb diet definitely has its party faithful, but how exactly does the low carb diet cause your body to burn fat? Earlier studies have shown that feeding rodents a low carb, high fat diet caused fat usage and weight loss, but the mechanism of the process wasn’t known.

Now two studies, published in the June 2007 issue of Cell Metabolism, have identified a hormone produced by the liver, fibroblast growth factor 21 (FGF21) that may help explain how that low carb diet causes you (or at least mice) to lose weight.

It’s apparently a missing link in the biology of fasting, and it works by inducing fat use and the production of ketone bodies by the liver. When mice were deprived of glucose by being fed an Atkins-type diet, it was FGF21 that stimulated their bodies to start burning fat stores.

Mammals survive famine by shifting from glucose as fuel to ketone bodies as fuel. Ketones are produced from fatty acids that have been stored in the liver for just such an eventuality. During prolonged starvation, ketones can provide up to half of an animal’s energy requirements and up to seventy percent of the energy for the brain. A high fat, low carb diet is called ketogenic because it causes the production of ketone bodies for energy.

The first study showed that increased blood levels of FGF21 are required for mice on a carb-restricted diet to begin burning fat. In the study, mice were fed a low carb high fat diet for thirty days; they lost weight, and the researchers found FGF21 was dramatically increased.

In mice genetically engineered to lack FGF21, feeding the same low carb high fat diet resulted in a fatty liver, high blood lipids, and reduced ketone bodies. The researchers concluded that induction of FGF21 in the liver is required for normal liver fat use, triglyceride clearance, and the production of ketone bodies brought about by a ketogenic low carb diet.

The second study showed that FGF21 is triggered by PPAR-alpha, which is already known to regulate use of fat as an energy source during famine. PPAR-alpha is the target of cholesterol-lowering drugs like LOPID. The researchers found that in mice on a low carb diet, FGF21 stimulated the breakdown of fat stored in white fat tissue and the liver’s production of ketone bodies.

In fact, high levels of the hormone mobilized fat even when the animals weren’t on a diet. In other words, animals given excess FGF21 responded like they were fasting even when they were getting fed plenty. FGF21 also caused the mice to slow down and conserve energy by entering a torpid state.

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Sources: Royal Society of Chemistry
Cell Metabolism
Southwestern Medical Center

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