BIOTECH: Master switch for hunger, reproduction, identified

A master switch that controls hunger and reproduction has been discovered -- in mice.

The switch for these primordial animal instincts likely also is present in humans, said Mark Montminy, a professor at the Salk Institute, in a telephone interview last week.

Further research could lead to new obesity and infertility treatments, said Montminy, who took part in a study identifying the molecular switch. The study was published Sunday in the online edition of the journal Nature Medicine.

The study examined what happens to mice when the gene that makes the master switch is disabled. These mice appeared normal at birth, but began to put on weight about eight weeks later. They also became resistant to insulin, a critical hormone that controls blood sugar.

Moreover, both male and female mice lacking the switch were found to be infertile.

Insulin resistance and obesity are characteristic of Type II diabetes, the most common form of the disease. Potential complications include heart disease, blindness, nerve and kidney damage.

Obesity and Type II diabetes are linked. As obesity has ballooned in the United States, so has the incidence of Type II diabetes. So any effective treatment that cures or prevents the disease would not only provide a major health benefit, it could be a huge money-maker.

About 18 million Americans have diabetes, according to the American Diabetes Association, and about 90 percent of those people have Type II diabetes.

Millions more are obese and in danger of developing diabetes. Controlling weight has been proven effective in reducing the severity of Type II diabetes.

Montminy said the master switch, which occurs in brain cells, gives the brain information that helps it regulate food intake and energy expenditure.

"The brain is the central processing unit for the organism, and it needs a way to know what's going on outside the brain, like how much food you're taking in and how much exercise you're doing," Montminy said. "It puts that all together and makes certain decisions, like will you be able to reproduce, or whether you can grow."

Lack of food is known to inhibit female reproduction, Montminy said. The organism conserves energy for survival, because it doesn't have enough to sustain itself and produce healthy offspring.

But in some cases, the brain receives incorrect information from the signals, Montminy said. He likened the miscommunication to a game of "telephone," in which a message relayed from person to person is progressively distorted. In such cases, drug therapy could help overweight or infertile people.

The master switch, called TORC1, is regulated by leptin, a hormone that tells the brain enough food has been consumed. Leptin is made from adipose, or fat cells. Mice lacking leptin became overweight, according a 1995 study that caused great excitement in the scientific community.

Biotech giant Amgen Inc. of Thousand Oaks licensed the discovery for $20 million from Rockefeller University, and tested a leptin-derived drug as an obesity treatment. However, the leptin drug had a relatively minor effect in humans, so Amgen discontinued testing.


