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Scientists Identify Four Candidate Obesity Genes in Mice

Article published in Physiologic Genomics

Bethesda, Md. (Sept. 6, 2011)—As obesity rates rise worldwide, researchers continue to look for ways to understand the causes of this complex condition. Though environment plays a powerful role, studies suggest that genes are also important players in promoting the disorder. Scientists have thus far identified dozens of genes that influence obesity in people. However, this is just a fraction of the number they believe exist.

Seeking to identify additional candidate obesity genes, a team of researchers at the University of California, Davis (UC-Davis) developed a mouse strain which they used to examine several novel genes that might influence obesity. Building on their earlier discoveries, they identified a stretch of eight genes in mouse chromosome 7 and found evidence that four of these genes may relate to obesity. Since humans have their own versions of these genes, the findings could help shed light on obesity in people.

The article is entitled “Four Out of Eight Genes in a Mouse Chromosome 7 Congenic Donor Region are Candidate Obesity Genes.” It appears in the Articles in Press section of Physiologic Genomics, published by the American Physiological Society.

Methodology

The researchers crossed for many generations a strain of mice that is more likely to be obese and a separate strain of mice that is genetically lean to create a new mouse strain.  This new mouse strain, named 318, contained a region of 8 genes from the obese mouse strain and the rest of its genes were inherited from the lean mouse strain. The 318 strain was obese even though most of its genes were inherited from the lean strain. They then tested the 318 strain to determine which of the 8 genes appeared to be responsible for obesity. Using a variety of analyses, they looked for differences in the expression levels of these genes in three areas; the brain, liver, and fat, since these tissues are key in influencing obesity. They also searched for mutations in these genes that might be responsible for promoting obesity.

Results

Ultimately, the researchers identified a section of mouse chromosome 7 containing eight genes that seemed to be responsible for causing obesity in the 318 strain. The results showed that only four of these genes differed in expression levels compared to the non-obese strain.

Three of these four genes showed different expression levels in female animals, and two showed expression differences in male animals. Depending on tissue type, some genes were more highly expressed than those in the non-obese strain, and others were expressed at lower rates. Only one of the genes differed in sequence from the non-obese strain, and only by a single nucleotide.

Importance of the Findings

The study authors suggest that any one or all four of the genes they identified could play an important role in obesity in people. However, since most of these genes had the same sequences as those in the non-obese strain, the differences in expression levels may be influencing obesity. According to Craig H. Warden, the senior author of the study, “Our study demonstrates the presence of at least four potential obesity genes in the 318 congenic but cannot definitely identify any one as the most likely candidate. The results are a demonstration that caution should be exercised when searching for obesity genes because comprehensive expression studies of linked adjacent genes will identify more candidates than will studies limited to a single tissue.” He said that further research will be necessary to understand the effects of these differences.

Study Team

In addition to Dr. Warden, who is affiliated with the UC-Davis Department of Pediatrics, the study team was comprised of co-investigators Kari A. Sarahan, of the Department of Neurobiology, Physiology and Behavior, and Janis S. Fisler of the Department of Nutrition.

NOTE TO EDITORS: The abstract and article are available online. To arrange an interview with Dr. Warden, please contact Donna Krupa at dkrupa@the-aps.org, 301.634.7209.

Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,500 members and publishes 15 peer-reviewed journals with a worldwide readership.