Researchers Uncover 'Obesity Gene' Involved in Response to High-Fat Diet

Scientists have determined that a specific gene plays a role in the weight-gain response to a high-fat diet.

The finding in an animal study suggests that blocking this gene could one day be a therapeutic strategy to reduce diet-related obesity and associated disorders, such as diabetes and liver damage, in humans.

The researchers found that a diet rich in fat induced production of this gene, called protein kinase C beta (PKC beta), in the fat cells of mice. These mice rapidly gained weight while eating a high-fat diet for 12 weeks.

On the other hand, mice genetically engineered to lack PKC beta gained relatively little weight and showed minimal health effects after eating the same high-fat diet.

In comparing the effects of the high-fat diet and a regular diet, the scientists found that mice fed the high-fat diet produced more PKC beta in their fat tissue than did mice eating a regular diet.

“So we now know this gene is induced by a high-fat diet in fat cells, and a deficiency of this gene leads to resistance to fat-induced obesity and related insulin resistance and liver damage,” said Kamal Mehta, senior author of the study and a professor of molecular and cellular biochemistry in Ohio State University’s College of Medicine.

“It could be that the high-fat diet is a signal to the body to store more fat. And when that gene is not there, then the fat storage cannot occur.”

Though the complete mechanism remains unknown, the research to date suggests that rather than storing fat, mice lacking the gene burn fat more rapidly than they would if the PKC beta were present, Mehta said.

The research is available online in the journal Hepatology and is scheduled for later print publication.

Mehta and colleagues previously had created the hybrid mouse model by cross-breeding mice deficient in PKC beta with the C57 black mouse, a common animal used in research for studying diabetes and obesity. Despite the propensity for obesity from their original genes, the new mice lost weight while eating up to 30 percent more food than other mice.

In the earlier study, the mice ate a regular diet. In this new study, the researchers fed PKC beta-deficient and normal mice either a diet in which 60 percent of calories were derived from fat – the high-fat diet – or a standard diet in which 15 percent of calories came from fat. In the typical American diet, about 40 percent of calories are derived from fat.

The normal mice on the high-fat diet showed weight gain within three weeks, a trend that continued throughout the 12-week study. The PKC beta-deficient mice on the same diet gained less weight even while appearing to be extra hungry and eating more calories than the normal mice – meaning their lower body weight was not the result of eating less.

Of animals eating the high-fat diet, the fat tissue and livers in the normal mice were larger than those in the PKC beta-deficient mice, as well. The livers of the normal mice were on average about 50 percent larger than the livers in mice lacking the gene. And the white fat tissue – the tissue in which PKC beta was expressed as a result of the high-fat diet – was almost three times as heavy in the normal mice as in the PKC beta-deficient mice.