“Luckily, at the time, Colorado State was conducting an arthritis study in dogs,” says Hannah.“We were able to put these dogs on test diets with different levels of omega-3 fatty acids and then analyze the joints.” They quickly found that they were indeed able to match the levels that they had gotten in the petri dish.
“That’s all nice,” says Hannah,“but the bigger question is whether the dog actually cares. Does it make a clinical difference?” That’s where force-plate analysis came in. This process determines whether a dog’s lameness has improved; researchers did find improvement in the dogs’ physical abilities.
“We were able to verify that the changes in the gene expression profile were accompanied by changes in the corresponding enzyme levels too,” says Hannah. “After the diet, the joints contained less metalloprotease, an enzyme that degrades the cartilage, and more protein that inhibited the metalloproteases. So the omega-3 down-regulated the enzymes that chew up cartilage and up-regulated factors that inhibit the degradation.”
Another major area of nutrigenomics research is in obesity. “We’ve looked at the gene expression profile in obese patients,” says Dr. Todd Towell of Hill’s Pet Nutrition.“We can see a huge difference in gene expression between dogs who are obese and those who are lean.”
What classes of genes are different? The short answer is that at the level of gene expression, obese dogs are up-regulated at systems that make them efficient at storing fat in adipose tissue. They are fat storers. Those who are lean are more efficient at burning fat for energy.
Armed with this information, researchers set out to answer the million-dollar question: Is it possible to design a diet that would both allow weight loss and change the gene profile? To find out, Hill’s researchers fed overweight animals a new weight-reduction diet and then looked at their gene expression profiles; they looked at percent of body fat and genomic analysis at the onset of the study and then again after four months on the diet. All the dogs went from overweight to lean, and those on the new diet showed a change in 254 genes—240 were down-regulated and 14 were upregulated. The diet had changed the dogs’ metabolisms from fat-storing to fat-burning.
Interestingly, in a similar study with dogs on a high-protein weight-loss diet, dogs also went from fat to lean, but their gene expression profiles remained those of metabolically obese dogs. So they were still fat-storers, which suggests they would gain weight back. Because it’s the gene expression in the fat cells that’s important, the downside to this study is that researchers tested the gene expression in blood cells but did not test it in the fat cells where fat is actually stored; their assumption was that gene expression was also changing in the fat cells.
Another researcher who has looked at gene-expression changes in fat is Dr. Kelly Swanson, adjunct assistant professor at the University of Illinois, Department of Veterinary Clinical Medicine. “We fed a fructooligosaccharide, which is a fiber-like substance that’s not digested by the host but preferentially stimulates the beneficial microbes in the gut.” In other words, the fructooligosaccharide hangs around in the gut, where it serves as food for beneficial microbes. As a result, it allows the beneficial microbes to flourish.
The results? The diet improved insulin sensitivity in fat cells of obese dogs. Several genes that coded for proteins important in lipid regulation and oxidation were up-regulated. These results suggest that a diet with fructooligosaccharides could be useful in diabetic patients.
These findings are just the start. Says Hannah,“Researchers are routinely using nutrigenomics to understand physiology and biology at a new level. Instead of just trying to find individual genes that predispose dogs to developing diseases such as diabetes or obesity, researchers are now asking, ‘What about all of the genes and corresponding pathways?’ It’s about understanding how a molecule or nutrient changes gene expression.”
Says Swanson, “With nutrigenomics, you often get to disease states you don’t understand. If you can identify the genes and pathways affected in the disease process and know the effect of nutrition on that same process, you can determine the biological mechanisms to target.”