Steele Children's Research Center Discovers that Decreased NPC1 Gene Function Has a Role in Early-Onset Weight Gain

Researchers at the University of Arizona College of Medicine Steele Children’s Research Center have found that decreased amounts of a particular gene leads to weight gain.
Researchers at the University of Arizona College of Medicine Steele Children’s Research Center have found that decreased amounts of a particular gene leads to weight gain. Their study, “Decreased NPC1 Gene Dosage in Mice is Associated with Weight Gain,” was recently published by the Nature Publishing Group journal, Obesity.
 
A previous study indicated that the Niemann-Pick C1 (NPC1) gene in humans was associated with early-onset morbid obesity, but it was unknown whether weight gain was a result of increased or decreased NPC1 gene function.
 
Led by William S. Garver, PhD (previously with the Steele Center, and now with the University of New Mexico Health Sciences Center), the research team fed a high-fat diet to mice with less-than-normal amounts of the NPC1 gene, in addition to mice with normal amounts of the NPC1 gene. The mice with decreased amounts of the NPC1 gene showed significant weight gain, while the control mice did not. “Our study demonstrated that a decreased amount of the NPC1 gene was associated with weight gain,” says Dr. Garver.
 
Since the mice with decreased amounts of the NPC1 gene fed a low-fat diet did not gain weight, the results suggested that the NPC1 gene interacted with a high-fat diet to promote weight gain.
 
"A number of large population-based studies have identified genes believed to be associated with obesity. However, our controlled study using mice with altered gene function confirmed and extended these results by determining that it was decreased amounts and function of the NPC1 gene that contributed to weight gain,” says Dr. Garver. “These results are significant because now the NPC1 gene may serve as a therapeutic target in the prevention or treatment of early-onset obesity."
 
This research was funded by grants received from the National Institutes of Health, the Tohono O’odham Nation, and other private donations. Other contributors to this study included David Jelinek, MS and Robert P. Erickson, MD, with the Steele Center, and Randall A. Heidenreich, MD, also from the University of New Mexico Health Sciences Center.
 
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The University of Arizona College of Medicine, University Physicians Healthcare and University Medical Center work together to care for patients, educate medical students, train resident-physicians and conduct clinical and basic research. The UA Steele Children’s Research Center and UMC are working together to build Diamond Children’s Medical Center (www.diamondchildrens.org), now under construction and scheduled to open in 2010. Diamond Children's will be Arizona’s only pediatric inpatient medical center connected to an academic research facility – the Steele Center (www.steelecenter.arizona.edu).