Diabetes, obesity metabolic link studied

U.S. medical researchers say they have discovered a key molecular partnership that coordinates body rhythms and metabolism.

University of Pennsylvania researchers led by Dr. Mitchell Lazar and doctoral student Theresa Alenghat said they studied a protein called NCoR that modulates the body's responses to metabolic hormones. They said they engineered a mutation in mice that prevents NCoR from working with an enzyme that's normally its partner -- HDAC3. 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.

The role of the NCoR-HDAC3 partnership in regulating the body's internal clock was previously unknown, the scientists said. 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 said their findings suggest HDAC via NCoR controls the body's internal clock, and, therefore, metabolism, through epigenetic change.

In the fight against the obesity and diabetes epidemics, disruption of NCoR and its enzyme partner might be a valuable new weapon, said Lazar.

The research is reported in the journal Nature.