U.S. Department of Health and Human Services

Removing a protein prevents obesity, extends lifespan in mice

Aging is associated with more body fat – also known as white fat – and less efficient use of energy. Exactly what influences these changes has been poorly understood. A team at NIDDK’s intramural Genetics of Development and Disease Branch led by Elisabetta Mueller, Ph.D., has found that deleting a protein named Foxa3 protects mice from developing obesity and type 2 diabetes as they age. Because mice without the protein were able to burn fat rather than accumulate it, they had an average of 40% less fat and a 67% lower risk of death after about two years than the mice with the protein. Additionally, much of the white fat in mice lacking Foxa3 turned into “brown-like fat,” generating heat and improving energy expenditure by burning rather than storing fat, thereby preventing the mice from becoming overweight.

The results suggest a new target for therapies to prevent age-associated onset of obesity and insulin resistance, a condition in which the body produces insulin but does not use it effectively. Obesity and insulin resistance increase the risk of developing type 2 diabetes.

The NIDDK researchers and collaborators at the NIH’s National Human Genome Research Institute are currently investigating whether the findings also apply to people.

The study published in PNAS on September 14.

infrared images from before the cold challenge and after the cold challenge

The infrared images compare tissue from mice with the protein (left) to mice without the protein (right) before and after being exposed to cooler temperatures to determine ability to generate heat. In each image, the tissue from mice without the protein shows more red and white areas, pointing to enhanced energy expenditure.

 
Credit: NIDDK Genetics of Development and Disease Branch