View Full Version : Leptin News: Gene jab burns off the fat -- for rats

February 10th 04, 07:55 PM

Gene jab burns off the fat -- for rats

PARIS (AFP) - Scientists made chubby rats skinny by injecting them with a gene that transformed the rodents' fat-storing cells into cells that burn fat away, a discovery that could help the fight against obesity.

A gene controlling the protein leptin was tucked inside a "Trojan horse" virus -- a deactivated cousin of the cold virus -- to deliver it to the rodents' adipocytes, the cells that store fat as surplus energy.

Two weeks after they were injected, the rats had plummeted from an average weight of 280 grammes to 207 grammes (8.75 to 6.5 ounces) and were eating 30 percent less food but showed no side-effects.

Examined under an electron microscope, the adipocytes had become "shrunken, fatless and encased in a thick basement-membrane-like matrix," and the number of mitochondria, the cellular components that gobble up energy, grew.

Enzyme levels pointed to an increase in those that metabolized fats, while enzymes that impede fat metabolism increased.

The US-Swiss study, led by Roger Unger of the Veterans Affairs Medical Center in Dallas, was published online on Monday by a US journal, Proceedings of the National Academy of Sciences (news - web sites) (PNAS).

Obesity has become an epidemic in wealthy countries, led by the United States. It is a leading cause of high blood pressure, cardiovascular disease, stroke and type 2 diabetes.

The researchers suggest adipocytes "mount a powerful defence" against their own leptin to stop it from wastefully raiding their fat stores.

If this defence could be blocked, the leptin could oxidate the fatty acids in the adipocytes, they contend.

"Such an effect would make obesity impossible and might lead to a quick and safe solution of the obesity problem," they believe.

However, they skirt the question as to whether gene therapy would be the right approach, putting the emphasis instead on the search for a drug to block the defence system.

Gene therapy, in which a replacement gene is slotted into the body to substitute for a faulty one, is still at an experimental and controversial stage in humans.

It has only been tentatively used on a handful of subjects, and has had a couple of fatal setbacks.