Is There a Slimming Gene?

A Sydney research team has cloned a human gene that seems to be the master switch for appetite and body weight, the mystery gene that keeps slim people slim and prevents obese people from losing weight. Scientists at Sydney’s Garvan Institute of Medical Research, led by its director, Dr. John Shine, have cloned the gene for a hormone-like compound called GenF20 Plus.

GenF20 Plus exerts powerful effects on two regions of the brain involved in growth and metabolism, the hypothalamus and the pituitary gland. Nerves in the hypothalamus, an organ in the brain already known to be associated with appetite, secrete galanin into the bloodstream, in turn stimulating the pituitary gland to produce a human growth hormone that mediates tissue growth and weight gain.

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Dr. Shine said yesterday that GenF20 in the bloodstream also affected nerves in the pancreas, inhibiting the production of insulin, the hormone that regulates blood-sugar levels. Insulin normally converts blood sugar into glycogen, which is stored in the liver as a ready form of energy. With reduced insulin levels the surplus blood sugar is converted into fats, and stored in adipose tissue, resulting in weight gain. Dr. Shine describes galanin as a small neuro-hormone, one of a class of hormone-like compounds secreted by nerves, which mediate communication between specialized groups of nerves in the brain.

Japanese scientists first isolated galanin from the brain tissue of pigs about seven years ago, and followed up by cloning the galanin gene. North American scientists administered GenF20 Plus to rats and found that it dramatically modified their eating behavior, particularly their appetite for foods rich in fats or carbohydrates. Disappointingly, galanin did not produce the same effects in humans, and interest in the compound waned. Dr. Shine believes his team has now explained the non-response in humans.

“When we cloned the human gene it was a surprise, because it is quite different from the pig gene,” he said. Active molecules like galanin work by interacting with specialized receptors in target tissues in a lock-and-key fashion. Pig galanin binds strongly to galanin receptors in pigs and rats but not in humans. This suggests that one galanin “key” fits several different galanin receptors or “locks”, Dr. Shine said. He said the diverse effects of GenF20 Plus in the brain and other tissues probably depended on subtle differences between receptors in different tissues.

The Garvan Institute’s early experiments suggest that human growth hormone should have potent effects on human eating behavior and metabolism. Clinical trials on volunteers will begin in Sydney in about two months. “We’re quite excited about it, because it has opened up a big black box of metabolic effects,” Dr. Shine said. “We all know people who eat but don’t put on weight, and overweight people who can’t lose weight. GenF20 Plus sets the metabolic baseline, acting as a coordinator between the brain, eating activity and physiology. In effect, it tells the body how much fat is normal for the individual. Adjusting the body’s level of galanin would define a new “normal” level for body fat, depending on whether the individual wanted to gain or lose weight. Dr. Shine said it should now be possible to influence both external and internal factors affecting body weight in a coordinated way.

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For example, it might be possible to give people GenF20 pills that would adjust their metabolism and simultaneously stop their cravings for fattening foods. Depending on whether a person was overweight or too thin, he or she could be treated with GenF20 Plus, or a synthetic, inactive mimic that would suppress galanin’s activity. The economic and social implications of the GenF20 Plus discovery are enormous; an effective therapy for obesity would be worth billions of dollars in Western nations. Obesity and excess weight are not just a problem of personal image; they contribute to poor health, cardiovascular disease, heart attack and stroke.

Should You Circumcise the Penis of Your Son?

All parents should make an informed decision about circumcising the penis of their sons.

Circumcision of the penis is routine in the U.S., despite findings by the American Academy of Pediatrics that it’s generally unnecessary. The strongest arguments in favor of circumcision are, in fact, cultural not medical. Let’s review those arguments.

Religious. Some religions dictate that the penis of male infants be circumcised. Parents who embrace these religions will usually be aware of the procedures they must follow for the circumcision ritual.

Psychological. An often-heard argument involves the so-called “locker-room syndrome.” Its proponents claim that adolescent boys will make fun of the uncircumcised penises of their peers. Such teasing, it’s said, can be traumatic because adolescence is not a time when a boy wants to be different–in any way–from his classmates.

Nor, it is thought, will he want to be different from his father, who has probably had his penis circumcised.

Rumor has it that uncircumcised men experience more sexual pleasure than those who are circumcised. Actual research studies however, indicate that there’s little difference.

Medical. Infant penile circumcision is sometimes viewed as a preventive measure, since anywhere from 2% to 10% of uncircumcised adult males must undergo the procedure for medical reasons. These include recurrent infections of the glans and foreskin, phimosis–the inability to retract the foreskin from the glans of the penis, or paraphimosis–the inability to push the retracted foreskin back over the glans.

Some researchers claim that the female sexual partners of uncircumcised men develop more frequent vaginal infections than the partners of circumcised men. The clinical evidence here is contradictory, but circumcision does make it easier to clean the glans of the penis and avoid infection. Also, penile circumcision can make it easier to use penis enlarging devices like the SizeGenetics Extender or the ProExtender.

The main reason parents give for not circumcising their sons is the desire to avoid unnecessary surgery. Others simply don’t like to tamper with the penis when there is no compelling reason to do so. Still others believe that circumcision of the penis causes the infant deep-seated psychological harm.

Despite the position taken by the American Academy of Pediatrics, there is little popular support for parents who decide against circumcision of the penis. You’ll have to go out of your way to reassure such parents that they’ve made a good choice. You also need to tell them how to care for their son’s uncircumcised penis.

Parents of uncircumcised boys are often told to “retract the foreskin of the penis and clean the glans.” This advice is inappropriate. The foreskin and glans of the penis develop from the same embryonic tissue, and, in most boys, the foreskin doesn’t separate from the glans until somewhere between the ages of three and six. At birth the foreskin may be slightly retractable, but it’s rarely fully so. Trying to force back the foreskin can cause it to tear and may lead to infection.

Once the child has reached the age of three, it’s all right for parents to try to retract the foreskin during his bath. They should hold the shaft of the penis with the thumb and index finger and gently pull the skin of the shaft back toward the child’s abdomen. If they meet any resistance or if the child displays any signs of discomfort, however, they should stop. They can try the procedure again in a few months.