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Can Diet Overcome DNA?
Scientists investigate the new field of nutrigenomics.
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Have you ever had problems losing weight and wondered if you’re just genetically fat and doomed to your pudgy fate? If so, you may be in luck. Scientists studying nutrition and genetics in dogs are helping to debunk the myth that your genes set your physiologic fate in stone.

“Your DNA tells you everything you could be. It doesn’t tell you everything you are going to be,” says Dr. Steven Hannah, Director of Molecular Nutrition at Nestlé Purina PetCare.“There are many factors that modify the ultimate expression of an animal.” One such factor is diet.

New studies are finding that diets can alter the expression of genes. In other words, they can determine which genes are active. In fact, there’s now a branch of nutrition called “nutrigenomics” dedicated to the study of how nutrients affect gene expression.

In an active gene, a segment of DNA is transcribed to RNA, which can then be translated into many copies of a single protein. Each gene codes for a different protein and each protein has a slightly different job. Some proteins provide structure, such as the protein in muscle or collagen.Other proteins, called enzymes, drive the chemical reactions that create the various hormones, neurotransmitters and products needed by the body, as well as creating products that serve as energy to power the body.

In humans, the study of nutrigenomics is slow because there are too many factors to consider in a person’s normal life—even in just their diet. But with dogs, researchers have already discovered diets that alter arthritis and obesity.

How does nutrigenomics come into play in developing these diets? First, the company or researcher identifies gene expression profiles in affected and normal dogs.Next, they figure out which ingredients they believe will change the gene expression profile from that of an affected dog to that of a healthy one. Then they formulate a mixture, feed it to the affected individuals and see if the gene expression profile changes in a positive way. For instance, in the case of arthritis or degenerative joint disease, researchers at Purina compared the gene expression profile of normal, healthy cartilage cells, called “chondrocytes,” to that of arthritic chondrocytes.

“We have constructed a gene expression array chip that has virtually every gene known in the dog,” states Hannah. “It has tens of thousands of genes on it. We took the chondrocyte cell’s RNA and applied it to the chip.” The chip, in turn, revealed every gene whose expression was affected.

“We were able to identify which genes in the tissue were up- and down-regulated in arthritis,” says Hannah.“Because those genes are codes for all of the proteins the cell was making, it’s a snapshot in time of what the cell is planning to do biochemically.” (“Up-regulation” and “down-regulation” are the processes by which cells increase or decrease, respectively, the quantity of a cellular component, such as RNA or protein, in response to an external variable.)

By examining the 325 up-regulated genes and the 25 down-regulated genes, Purina researchers were able to look at the biochemical decision of the arthritic cell compared to a healthy chondrocyte cell. What they found was that the arthritic cells were up-regulating specific enzymes that degrade the cartilage and down-regulating enzymes that inhibit the degradation process. That is, they were primed for cartilage destruction.

The next step was to determine what dietary changes might affect the joint. These tests started in petri dishes. First, the researchers grew chondrocytes in cell culture and added inflammatory mediators that would be seen with any joint injury. This made the chondrocytes look arthritic. Then they added nutrients at various concentrations to see which nutrients would help the cells repair.With that testing, they found that omega-3 fatty acids provided good results, and they were able to determine which levels worked best.

But, as Hannah points out, “We can’t feed the nutrient directly into an animal’s joint. There’s no cell culture dog food. Rather, we needed to next see if we could get the nutrient from the food in the same concentrations into the dogs’ joint.”They needed to know if the fish oil would be digested, absorbed and then the omega-3 fatty acids transported to the joint in concentrations shown to be effective in the cell culture.

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