A new study by a team of University of Notre Dame researchers, which appears in the Sept. 2 edition of the journal PLoS ONE, is a significant step in understanding the molecular genetic and physiological basis for a spectrum of metabolic diseases related to circadian function.
Obesity and diabetes have reached epidemic levels and are responsible for increased morbidity and mortality throughout the world. Furthermore, the incidence of metabolic disease is significantly elevated in shift-work personnel, revealing an important link between the circadian clock, the sleep-wake cycle, time-of-day feeding and metabolism.
Given that more than 16 percent of the U.S. and European work force engage in shift work, an understanding of the development of elevated metabolic disorders in shift work is critical. Also, there are sex differences in the incidence of metabolic diseases, with obesity occurring more frequently in women, and mortality rates for diabetes being higher in women. Understanding the molecular basis for these differences also is important.
The new study conducted by a team of researchers led by Giles Duffield, associate professor of biological sciences and a member of the Eck Institute for Global Health at Notre Dame, undertook a series of discrete behavioral and physiological experiments to determine the relationship between the circadian system and glucose metabolism. His group has been studying an important gene called "Inhibitor of DNA-binding 2" or Id2. The Id2 gene encodes a transcriptional repressor protein, whose normal job is to bind to specific transcription factor proteins and in turn reduce their operational activity. Removing Id2 from the biological system therefore impacts the switching off and on of other downstream genes.
The researchers examined glucose homeostasis and feeding/physical activity activity patterns in "knockout" mice that did not express the Id2 gene. Their analysis of the Id2 knockout mice provided
|Contact: Giles Duffield|
University of Notre Dame