Mouse on hand of researcher 

Studies in mice provide the foundation for much of the belief that high-fat diets are detrimental to human health. However, the majority of studies on the health effects of high-fat diets in mice published in five respected scientific journals in 2007 were not accurately portrayed, a survey by researchers at UC Davis has found.

"The bottom line is, unless the studies we do on mice are appropriately designed, we can't use the information to give people recommendations on diet," said study co-author Craig Warden, a professor of pediatrics and neurobiology, physiology and behavior in the Rowe Program on Genomics.

The survey results are described in a commentary published in the April 2008 issue of the journal Cell Metabolism. The commentary discusses research utilizing high-fat mouse diets that was published in 2007 in the journals Cell Metabolism, Diabetes, The Journal of Clinical Investigation, Nature and Nature Medicine.

These studies' major failing, Warden said, is comparing mice fed high-fat "defined" diets, often consisting of 60 percent lard, 20 percent sucrose and 20 percent casein or milk protein — the mouse equivalent of "pork rinds, ribs and Coke" — with mice fed a vegetable-based high-fiber "undefined" diet called chow composed of varying amounts of carbohydrate, fat and protein.

Craig Warden © UC Regents"This is a call to conduct diet studies correctly, because unless we get them right, they're meaningless."
— Craig Warden, study co-author

"Many papers using animal models draw conclusions about dietary effects from the comparison of natural-ingredient chow with defined diets, despite marked differences in micro- and macronutrient content," the commentary says. "When comparing the effects of a chow diet with a high-fat diet the effects of the dietary fat will be confounded with the effects of other components in the diet."

Warden added that two important differences between chow and high-fat defined diets are the contents of soy and sucrose. Chow is made from varying amounts of soy, which contains plant estrogens that affect food and water intake, anxiety-related behaviors, activity levels and the development of adipose tissue, or fat. And the sucrose in the high-fat diet has been linked to weight gain and insulin resistance. These factors are not taken into consideration when comparing the high-fat and chow diets.

Of the 35 studies surveyed, only five, or 14 percent, got it right. Forty-three percent of papers derived conclusions about effects of high-fat diets from comparisons of chow to a defined high-fat diet. Thirty four percent presented data without enough information to evaluate diet comparisons, because the publications did not provide details on diet. In 9 percent of the studies, both chow and high-fat diets were used but no direct comparison was made between the two.

"I and my collaborators were stunned that a majority of the literature used inappropriate comparisons of chow to defined diets or used unspecified diets," Warden said "Many of the reports from the animal-model literature have mischaracterized the effects of fat and carbohydrate on obesity and many other traits and diseases. This is a call to conduct diet studies correctly, because unless we get them right, they're meaningless."

Warden's research uses molecular genetics techniques in mouse models to study the impact of natural genetic variants on obesity and on response to diet and exercise. He has identified a protein that alters levels of hypothalamic alpha-melanocyte stimulating hormone (alpha-MSH) — a natural food intake inhibitor. This protein is a potential drug target because inhibitors decrease hunger. He also studies whether some people are genetically programmed to fail to maintain weight loss following gastric bypass surgery.

Collaborating with Warden on the commentary is Janis S. Fisler, associate, Department of Nutrition, UC Davis. The research was funded by a grant from the National Institutes of Health (NIH) and the Robert C. and Veronica Atkins Foundation.

UC Davis Health System is an academic medical center that includes a top-ranked school of medicine, a 577-bed acute care hospital, the proposed Betty Irene Moore School of Nursing, a National Cancer Institute-designated cancer center, the unique M.I.N.D. Institute for the study of neurodevelopmental disorders, a comprehensive children's hospital, a level 1 trauma center and outpatient clinics in communities throughout the Sacramento region. Consistently ranked among the nation's top medical schools and best hospitals, UC Davis has established itself as a national leader in telehealth, rural medicine, cancer, neurodevelopmental disorders, vascular medicine, and trauma and emergency medicine. Other areas of research strength include clinical and translational science, regenerative medicine, infectious disease, neuroscience, functional genomics and mouse biology, comparative medicine and nutrition, among many others.