September 04, 2007
Adipose Gene Controls Weight Gain And Loss

Genetic engineering as the solution to weight control problems?

“From worms to mammals, this gene controls fat formation,” said Dr. Jonathan Graff, associate professor of developmental biology and internal medicine at UT Southwestern and senior author of a study appearing in the Sept. 5 issue of Cell Metabolism. “It could explain why so many people struggle to lose weight and suggests an entirely new direction for developing medical treatments that address the current epidemic of diabetes and obesity.

...

In the current study, the UT Southwestern researchers examined how adipose works by analyzing fruit flies, tiny worms called C. elegans, cultured cells, and genetically engineered mice, as well as by exploiting sophisticated molecular techniques. Using several methods, they manipulated adipose in the various animals, turning the gene on and off at different stages in the animals’ lives and in various parts of their bodies.

It was discovered that the gene, which is also present in humans, is likely to be a high-level master switch that tells the body whether to accumulate or burn fat.

In the mice, the researchers found that increasing adipose activity improved the animals’ health in many ways. Mice with experimentally increased adipose activity ate as much or more than normal mice; however, they were leaner, had diabetes-resistant fat cells, and were better able to control insulin and blood-sugar metabolism.

In contrast, animals with reduced adipose activity were fatter, less healthy and had diabetes.

Scientists might be able to find a drug that turns up the expression of adipose. Such a drug might cause weight loss.

Flies and mice react the same ways to higher and lower levels of adipose gene expression.

To explore Adp’s function even further, Graff and his colleagues produced a strain of mutant flies like those that Doane had found years earlier. They found that the mutant flies were indeed fat and also had trouble getting around. Flies with only one copy of the Adp mutation fell somewhere in between the fat and normal flies, evidence that the gene’s effects are “dose dependent,” they reported.

Treatments that increased Adp in the insects’ fat tissue led them to lose weight, evidence that the gene operates within fat cells themselves. In mice that expressed the gene in fat-storing tissues, the same patterns emerged.

“We made mice that expressed Adp in fat-storing tissues, and lo and behold, what happened"” Graff said. “They were skinny—weighed less with markedly less fat—and their fat cells were smaller.” Smaller fat cells usually translate into better metabolic function, he said, including better blood sugar control.

Imagine the selective use of gene therapy to turn up the adipose gene in some tissue and turn down adipose in other parts of the body. It could be used to sculpt desired body shapes.

Share |      Randall Parker, 2007 September 04 11:55 PM  Brain Appetite


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