UT Southwestern Medical Center researchers conducted a study, recently published in the Proceedings of the National Academy of Sciences, that suggests sterile alpha motif domain containing protein 4 (Samd4), an unknown gene prior to this study, plays a major role in metabolism regulation. With these findings, researchers could provide new insights into diseases ranging from diabetes to obesity.
Dr. Zhe Chen, lead researcher and assistant professor of Biophysics, and Dr. Bruce Beutler, Nobel Laureate professor of immunology, both with UT Southwestern’s Center for the Genetics of Host Defense, analyzed mice with a Samd4 mutation, which they named “Supermodel.” This mutation protected homozygous mice (those who have hereditary pairs of genes) from high fat diet-induced obesity, likely by promoting enhanced energy expenditure through uncoupled mitochondrial respiration.
As a result, the “Supermodel” mice presented a lean phenotype — the observable characteristics of an organism. The mice were very small in size and had myopathy, a muscular disease, with an unusual body form caused by abnormal distribution of fat, excessive energy expenditure despite diminished cage activity, and impaired glucose tolerance.
“This mouse is important because it has revealed a new regulatory protein that’s very important for normal metabolism, but was never known to exist before,” explained Dr. Beutler, in a press release from UT Southwestern.
The study provides evidence that Samd4 modulates the activities of the mechanistic target of rapamycin complex 1, a master regulator of metabolism. Ultimately, Dr. Beutler adds, these results can be useful for diabetes and obesity research, the study of wasting in chronic disease and the study of muscle cell function, among other fields.
While at the Scripps Research Institute, Dr. Beutler developed a mouse mutagenesis program, which was continued at UT Southwestern and became the largest and most technologically advanced in the world. The new mouse phenotype was discovered in the lab’s colony of mutant mice several years ago, but the mutation was discovered and studied entirely at UT Southwestern, in a collaboration that also involved researchers Dr. William Holland, Assistant Professor of Internal Medicine, Dr. Aktar Ali, Assistant Professor of Internal Medicine, and John Shelton, lab manager in Internal Medicine.