The guilty enzyme, 11-HSD-1, produces cortisol, the fight-or-flight hormone that helps people survive in stressful situations. But it also produces cortisol in cells not normally associated with the hormone. An elevated level of cortisol is linked to visceral weight gain. Thus, an increase in this enzyme raises cortisol production, which leads to obesity and obesity-related diseases.

To analyze the metabolic activity behind visceral obesity, lead author Jeffrey S. Flier, a professor at Harvard Medical School, and his research team at Beth Israel Deaconess Medical Center observed the weight patterns of patients with an abundance of cortisol in their blood. Flier hypothesized that viscerally obese patients may be producing an abnormally high amount of cortisol by means of excess 11-HSD-1.

To test his hypothesis, Flier and his researchers created a group of transgenic (Tg) mice that overproduced the enzyme in about the same quantities they had previously observed in obese humans. These Tg mice were then compared with a group of non-Tg mice.

During the first nine weeks of life, both groups were fed low-fat diets, and their body weights remained the same. After this initial period, however, the Tg mice began to steadily gain weight—by 15 weeks of age they weighed 16% more than the non-Tg mice. The Tg mice also were more sensitive to weight gain when both groups were fed a high-fat diet, and they showed a significant weight gain in the abdominal region.

Researchers were surprised that it took only a modest increase of the 11-HSD-1 enzyme to cause the mice to become viscerally obese. They added that these animals eventually developed diabetes and became insulin-resistant, in addition to eating more.

“Obesity is a massive problem in our population,” said Flier in a statement released by the medical center. “If we could attack obesity, not only would people feel better, it would also improve all of these other disease states.”