Gene Disruption May Cause Adult-Onset Obesity

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Washington: A new study has found that disrupting one type of the gene ubiquitin (Ubb) in mice, may cause neuronal death in the hypothalamus, impaired control of energy balance and adult-onset obesity.

The study conducted by Xin-Yun Lu, Ph.D., assistant professor in the Department of Pharmacology at The University of Texas Health Science Center at San Antonio in collaboration with Stanford University, may have implications in finding a method to treat obesity and neurodegeneration.

"Ubiquitin is a small protein in the cell that marks unwanted proteins for destruction. This study shows that the deletion of a ubiquitin gene, Ubb, caused neurodegeneration in the hypothalamus, an important brain area for maintaining energy homeostasis. Mice with the Ubb gene deficiency have normal appetite but store fat more efficiently," said Lu.

It was found that adult mice with no functioning copies of the Ubb gene were fatter during their life span as compared to adult mice with one or both functional Ubb copies.

At the age of 1 month, the Ubb-deficient group had 20 percent fat content as against 18 percent in the Ubb-functional group. At 4-7 months, the Ubb-deficient mice had 45 percent fat content in comparison to 33 percent in the Ubb-functional group. And by the age of 10 months, the Ubb-deficient mice had 52 percent fat content compared to 37 percent in the Ubb-functional group.

It was also found that counts of hypothalamic neurons did not show any difference in 1-month-old mice in both groups. But by 3 months of age, the rodents in the Ubb-deficient group had 30 percent less hypothalamic neurons than their healthy peers.

According to Alan Frazer, Ph.D., chair of the Department of Pharmacology at the UT Health Science Center, the results are "both novel and important. They indicate that decreasing ubiquitin availability leads to neuronal cell death in the brain and causes obesity. This finding may lead to the development of novel therapeutic approaches to treat these disorders."

The findings of this study are described in the recent online Early Edition of the Proceedings of the National Academy of Sciences, U.S.A

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