May 19, 2011, Updated September 12, 2012

Israeli scientists believe that suppressing a certain brain protein could help obese people lose weight – but the tactic seems to work only for females.

Obesity in women research

By curbing the PTPe protein, Israeli scientists believe that it could lead to weight loss in women.

A protein called tyrosine phosphatase epsilon (PTPe, for short) plays a key role in obesity, according to study results published in the journal Cell Metabolism by researchers at Israel’s Weizmann Institute.

Prof. Ari Elson and his team in the institute’s molecular genetics department made the discovery when working with female mice that were genetically engineered to lack PTPe. Originally intending to investigate osteoporosis, they had removed the mice’s ovaries. This typically causes mice to gain weight to the point of obesity.

However, the scientists were surprised to find that the genetically engineered mice remained slim. Even after eating a specially formulated high-fat diet, they burned more energy and had more stable glucose levels as well.

Suspecting that the lack of PTPe had something to do with it, the scientists took a good look at the hypothalamus, a region of the brain that takes in assorted stimuli, including a wide variety of hormones, and sends out messages in the form of new hormones and nerve signals. They already knew that the hypothalamus is important in the complex balancing act of regulating body mass.

Elson and his team found that PTPe blocks the messages from a hormone called leptin, which reduces appetite and increases physical activity. Though it may seem counterintuitive, obese people often produce too much leptin. That’s because their body cells become resistant to its effects, and the brain generates more in an effort to compensate.

Apparently, PTPe plays a role in this resistance. The mice lacking the protein were highly sensitive to leptin and remained so despite aging, ovary removal and high-fat diets.

The bottom line? In obese humans with leptin insensitivity, inhibiting PTPe might help to reestablish a normal leptin response and in turn induce weight loss. Further research will need to be done to ensure that this strategy produces the same result in humans with no dangerous side effects.

Even if it turns out that PTPe suppression is a key to weight loss, though, it will likely apply only to females.

“Interestingly enough, the effect seems to be gender-specific,” said Elson, who heads the Weizmann’s Ekard Research School of Biological Science and Lorry I. Lokey Research School of Biochemical Science. “Male mice hardly benefited at all from the lack of PTPe compared with the female mice. This finding could open up whole new lines of inquiry in obesity studies.”

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