05.21.2001 – Health Scan: Overweight? It’s all in your head

By JUDY SIEGEL-ITZKOVICH
LAST UPDATED: 05/21/2011 23:13

Weizmann Institute researchers have added another piece to obesity puzzle, showing how, why a certain brain protein contributes to weight gain.

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PHOTO: REUTERS

If you are very overweight and always thought it was something in your head, you were right – but it is not just psychological; it is something in a small part of the brain. Weizmann Institute of Science researchers have added another piece to the obesity puzzle, showing how and why a certain brain protein contributes to weight gain. Their work was published in Cell Metabolism.

Prof. Ari Elson and his team in the Rehovot institute’s molecular genetics department made the discovery when working with female mice that were genetically engineered to lack protein tyrosine phosphatase epsilon (PTPe). As the scientists had originally intended to investigate osteoporosis, they also removed the rodents’ ovaries. Oophorectomy typically causes mice to gain weight to the point of obesity – so the scientists were surprised to find that the weight of the genetically-engineered mice remained stable. Working with Dr. Alon Chen and his group in the neurobiology department and Prof. Hilla Knobler, head of the unit of metabolic disease and diabetes of Kaplan Medical Center in Rehovot, the researchers fed these mice a high-fat diet, yet the PTPe-deficient mice maintained their svelte figures; they burned more energy and had more stable glucose levels as well.

To find out how the lack of this protein could keep mice slim and healthy, the scientists looked at the hypothalamus – a region of the brain that takes in assorted stimuli, including a wide variety of hormones, and sends out messages of its own in the form of new hormones and nerve signals. The hypothalamus plays a vital role in regulating body mass – a complex balancing act that involves, among other things, controlling appetite and physical activity.

Elson and his team found that PTPe blocks the messages from a now-well-known hormone called leptin – a key player in body mass regulation. They revealed exactly how it does this: PTPe responds to the leptin signal in the hypothalamus, inhibiting certain molecules, which in turn dampens that signal.

Among leptin’s activities is that it reduces appetite and increases physical activity. Paradoxically, obese people often have a surfeit of leptin in their blood. This is because, while their bodies produce the hormone normally, their cells become resistant to its effects, and more leptin is generated to compensate. The new research shows that PTPe plays a role in this resistance. The team found that mice lacking the protein were highly sensitive to leptin; and they remained so despite aging, ovary removal or high-fat diets. This suggests that in obese humans with leptin insensitivity, inhibiting PTPe might, conceivably, help reestablish the leptin response and induce weight loss. This, however, requires further research to ensure that it acts in the same way in humans, with no dangerous side-effects.

Elson noted: “Interestingly enough, the effect seems to be gender-specific. Male mice hardly benefitted from the lack of PTPe compared with female mice. This finding could open up whole new lines of inquiry in obesity studies.”

HELPING AIDS CARRIERS BECOME PARENTS Having HIV, which is serious but has become a chronic disease, is not the end of the world. In fact, it could lead to the beginning of life. Four successful pregnancies were recently produced for still-healthy carriers by doctors at Jerusalem’s Hadassah University Medical Center . So far, 45 couples have registered for the new project for fertility in HIV carriers.

Dr. Keren Olstein, who coordinates it and follows up couples through the whole process, said success “is a dream-come-true for us” as well as the parents.

The women are healthy; their male partners are HIV carriers. To be accepted by the project, the couples must have taken the HIV drug cocktail of protease inhibitors for at least six months and present at least two tests with documentation of a low viral load in their immune systems. Then, the man gives a semen sample that is carefully rinsed in a Hadassah lab to remove all signs of the potentially deadly virus. If virology tests show there is no HIV in the semen, it is injected into the woman’s womb when she has ovulated. Prof. Shlomo Ma’ayan, head of the hospital’s AIDS clinic, initiated the project and receives assistance from staff of the IVF Center and of the Virology Lab.