Treating and Preventing Obesity = Two Different Things

Scientists have prevented obesity – in mice.

In two separate studies published in Gene Therapy and Molecular Therapy, researchers at UGA’s College of Pharmacy used gene injections to stop weight gain in mice that were fed a high fat diet. 

In the first study, the researchers injected a group of mice with the gene that codes for adiponectin. In the second study, another group of mice were injected with the gene that codes for interleukin 10. The injections boosted expression of the genes and increased circulating levels of the desired molecule.

Scientists found that in mice fed a high fat diet, injections of either adiponectin or interleukin 10 suppressed the accumulation of fat and prevented the mouse version of type-2 diabetes – which is associated with obesity in humans.

Animals fed a well-balanced diet (regular chow) did not show any differences with either one of the genes.

So, do these injections help those who have already packed on the pounds?

Yongjie Ma, lead author of the adiponectin study, said that both injections failed to help obese mice lose weight. With 35.7 percent of adult Americans already obese, according to the CDC, the researchers’ goal is to find one or more genes that can help people burn off fat and lose weight. 

Turns out, treating obesity and preventing obesity are two different challenges.

“With prevention, you can just reduce lipogenesis (the synthesis of fat),” Ma said. “With treatment, if you reduce lipogenesis, it doesn’t work. You really need to stimulate lipolysis (breakdown of fat) and maybe trigger more energy expenditure.”

He said researchers also need to optimize their method for injecting genes to ensure that the technology is safe and effective for people.

The procedure involves pasting a specific gene into tiny rings of DNA called plasmids. The plasmids are added to about 2 milliliters of salt water, roughly 8 to 10 percent of the mouse’s lean mass, and then injected into the tail vein in 5 to 7 seconds.

The force of the injection causes the liquid to blast through cell membranes. The plasmids containing the gene can now freely enter the cell where the gene will provide the instructions to make the molecule it codes for.  

Currently, the researchers are trying to adapt the method in animals closer to humans, such as pigs and monkeys, to discover whether the procedure is likely to be safe and effective for people.

Instead of injecting into the tail vein, the researchers make a small incision in the neck and thread a catheter through the jugular vein and into the liver.

Ma said they still need to figure out the exact volume that will yield maximum gene expression. Because the genes are going straight into the liver, injecting a large amount of liquid will not be safe. They need to make the gene more concentrated and inject a smaller amount of liquid.

Ma and his colleagues hope to eventually bring their gene therapy method to the clinic. Ma said there aren’t many effective options for obese people right now. Surgery is mostly reserved for severe cases, and diet and exercise simply do not work very well.

“We need to provide more choices in this area,” Ma said. “Gene therapy is one choice.”

Mingming Gao is the lead author of the interleukin 10 study. Gao and Ma are members of Dexi Liu’s laboratory group at the Department of Pharmaceutical and Biological Sciences at UGA’s College of Pharmacy. Other collaborators include Chunbo Zhang, Le Bu, and Linna Yan.