Foie Gras. Liver cells in a normal mouse (left) and a mouse with its fatty acid synthesis gene knocked out (right), both fed a zero fat diet. The knockout mouse's liver rapidly accumulates fat (red) from other parts of the body.

Fresh Fat is Good Fat

A supply of fresh fat--either taken from food or built from body sugars--is necessary for a healthy metabolism, according to a new study. New fat triggers liver activity that results in healthy blood sugar and fat metabolism in a way that stored fat can't. The findings may lead to the identification of specific fats that could be taken to control heart disease, obesity, and diabetes.

After food is broken down, nutrients travel from the gut to the liver, where they are burned, stored, or processed and sent to other parts of the body. The liver controls levels of blood sugar and blood triglycerides--a form of fat. Abnormalities in these levels are associated with problems such as obesity, diabetes, and heart disease. Clay Semenkovich, an endocrinologist at Washington University in St. Louis, Missouri, and colleagues wanted to know more about how such levels are controlled.

To tackle the problem, the team genetically altered mice, "knocking out" a pathway that allows their livers to synthesize new fat. When fed a normal diet, the knockout mice were similar to their normal counterparts in body weight, body fat, and metabolic rate. But when fed a fat-free diet, the knockout mice rapidly lost weight and developed fatty livers and hypoglycemia, or low blood sugar. This happened, report the researchers, because stored fat headed to the liver from other parts of the body in response to fat starvation, but, to the researchers' surprise, the "old" fat could not trigger a known regulatory switch that activates fat breakdown to produce blood sugar.

The researchers could rescue the mice by restoring fat to the diet or providing them with a drug that turns on the regulatory switch, they report today in Cell Metabolism. The findings suggest liver cells are organized in such a way, Semenkovich says, that new fat can trigger healthy fat metabolism in the cell, but old fat can not. Semenkovich hopes to identify or engineer fats that would activate the regulatory switch, boosting fat metabolism to protect against obesity, diabetes, or heart disease.

The research is an important contribution to an emerging understanding of lipid metabolism, says physician Roger Unger of the University of Texas Southwestern Medical Center in Dallas, who studies diabetes and obesity. But it doesn't suggest we should reach for the French fries. "The most common cause of fatty liver today is obesity and overeating," he says, not lack of fat intake.

Related sites
The study
Semenkovich's Web site
Unger's Web site

Posted in Biology