London, Nov 27 : Scientists at University of Pennsylvania School of Medicine have discovered a key molecular partnership that coordinates body rhythms and metabolism.
For the study, the research team led by Mitchell Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism, studied a protein called NCoR that modulates the body's responses to metabolic hormones.
They then engineered a mutation into mice that prevents NCoR from working with an enzyme that is normally its partner, HDAC3.
It was found that the animals showed changes in the expression of clock and metabolic genes, and were leaner, more sensitive to insulin, and on different sleep-wake cycles than controls.
Scientists already know the role of the NCoR-HDAC3 partnership in regulating the body's internal clock.
HDAC3 is an enzyme that affects gene expression by binding to receptors in the cell nucleus to affect genes' activity, but not by directly changing DNA.
The researchers deduced that by using NcoR, HDAC controls the body's internal, and therefore metabolism, through this epigenetic change.
"In the fight against the obesity and diabetes epidemics, disruption of NCoR and its enzyme partner, might be a valuable new weapon," Nature quoted Lazar as saying.
Abnormal sleep patterns, such as those of shift-workers, can be risk factors for metabolic disorders such as obesity and diabetes.
"These diseases have reached epidemic proportions, so scientists are urgently seeking to understand the connections between biological rhythms and metabolism," said Lazar.
"The molecular partnership regulates hormone action as well as clock genes that coordinate circadian rhythms. It's extraordinary that, despite their abnormal sleep-wake cycle, which might have been predicted to cause metabolic problems, the mice were actually healthier metabolically," said Lazar.
He added: "However this finding doesn't mean people should start changing their sleep patterns because this is really evidence that there is coordination between metabolism and circadian activities, including sleep. It's not that the mice are sleeping less, it's that their sleep cycle is shifted, when compared to mice maintained on a normal sleep-wake cycle."
Now companies are targeting enzymes like HDAC with drugs called histone deacetylase (HDAC) inhibitors.
The findings of the study are reported in the latest issue of Nature.