Diet/gene breakthrough

Photo: John McNamara and Jennifer Sumner in WSU Pullman’s Knott Dairy Center. (Photo by Becky Phillips)

In the first study to show that a specific nutrient could alter the expression of genes in the body fat of dairy cattle, John McNamara and Jennifer Sumner have raised the bar for animal production standards while adding to the greater understanding of human health issues.

McNamara, professor in the Department of Animal Sciences and (intercollegiate, multidisciplinary) Nutrition Program, and Sumner, his doctoral student and postdoctoral research associate, have demonstrated that chromium in the diet changes the metabolism of body fat in dairy cattle by stimulating the expression of certain genes while simultaneously decreasing the expression of others.

Though it had long been known that the mineral chromium is required in the diet for good health in both animals and humans, the specific role it played in fat metabolism and milk production had not been described.

Adipose tissue is key
For more than 20 years, McNamara and his team have been working to identify genetic factors related to efficient milk production in dairy cattle. Knowing that adipose (fat) tissue plays an active role in successful reproduction and lactation, they centered their studies on identifying the metabolic functions of body fat. One of their main goals was to identify cows that gained neither too much nor too little weight during pregnancy and lactation.

“When cows store too much body fat, energy is diverted away from milk production and instead goes toward storing more fat,” McNamara said. “Yet if a cow does not store enough fat — or loses it too quickly — her immunity is impaired, causing inefficient production and leading to diseases like ketosis, milk fever and mastitis. Adipose tissue, in addition to being a major energy storage organ, is also a source of several powerful hormones that control food intake, inflammation and immunity.”

Chromium supplementation
In 2003, McNamara expanded his focus to include how cows vary in their use of specific nutrients — particularly in the time just before and after giving birth. His research showed that chromium supplementation increased feed intake and milk production in dairy cows.

“The unique part of this work was showing that chromium changed the body fat metabolism. It actually caused the cows to gain a little fat, which allowed them to make more milk but also prevented them from losing too much fat — it’s a very fine balance.”

The work had been funded by Kemin Industries, Inc., a nutritional ingredient manufacturer in Iowa. The company, intrigued with the results, wanted to know if chromium was affecting gene expression in fat metabolism. Using adipose samples from their previous studies, McNamara, Sumner and the Kemin team extracted the RNA and ran microchip array analyses to determine gene function. The study convincingly showed that chromium supplementation “upregulated” a number of genes — causing them to become more active — while others were “downregulated.”

This is the first study to document nutrigenomic activity in the body fat of dairy cattle. A provisional patent application for the discovery has been filed by McNamara and Kemin Industries.

Basic mammalian biology
At the same time, Sumner was conducting a companion study to measure gene activity in the adipose “lipolysis pathway” — which follows the breakdown and mobilization of fat tissue — a major contributor to milk production. Her work proved — also for the first time — that the point of highest gene activity coincided with the point of greatest lipolysis.

In essence, she confirmed that five major genes were upregulated during lactation, allowing the cow to utilize stored body fat for milk production.

“This is a novel finding for any mammalian species,” said McNamara.

These breakthroughs won McNamara and Sumner an invitation to the International Symposium on Energy and Protein to be held in Paris in September. They also garnered McNamara a grant from the U.S. Department of Agriculture and National Research Initiative to continue his work.

“Now that we’ve confirmed one application of nutrigenomics in dairy cattle, we plan to study it in more depth,” he said. “We can start to define exactly how genes in adipose tissue respond to different diets. It all comes back to the goal of breeding the most efficient animals for milk production.”

New world of nutrition
Is it nutrigenomics … or nutrigenetics? Either way, the goal of these emerging fields of nutrition is to optimize health — for both people and animals — through personally tailored diets. With the availability of biotechnologies developed in the genomic era, nutritionists can take the study of the relationship between genes, diet and health to a new level.

• In nutrigenomics, the basic goal is to discover how diet affects metabolic pathways in the body and how this regulation may be disturbed in diet-related disease — i.e., humans with a certain mutated gene absorb higher levels of fat from the intestine, leading to elevated cholesterol and possible atherosclerosis.

• In nutrigenetics, the aim is to understand how genetic makeup determines response to diet and susceptibility to diet-related disease — i.e., a number of genetic variations have been shown to increase the susceptibility to Type 2 diabetes, obesity, cardiovascular diseases and some autoimmune diseases and cancers.