New therapeutic avenues for obesity and diabetes.

© 2011 EPFL

© 2011 EPFL

NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function.

The Auwerx laboratory at the EPFL together with groups in San Diego (Salk Institute and UC San Diego) and UNIL publish two papers in Cell which highlight on the roles of a nuclear receptor co-repressor, NCoR1. Very little is known about how co-repressors, which inhibit gene transcription function and hence brake gene expression, work in the animal. In two independent studies both involving the Auwerx laboratory, now investigators address the function of the co-repressor NCoR1 in two different tissues, muscle and fat tissue. Interestingly, the absence of NCoR1 in muscle or adipose tissue leads to improved function of both tissues.
In the muscle the absence of NCoR1 leads to increased muscle mass, as you would expect if you omit an inhibitory factor. Interestingly, NCoR1 not only inhibits muscle mass but also seems to inhibit muscle function. Animals that lack NCoR1 in the muscle become really super performers - “marathon” animals - and move better and significantly longer. The EPFL team showed that this effect of NCoR1 is remarkably conserved in evolution from worms to mice. “Inhibitors of NCoR1 function could hence be of value to treat diseases with impaired muscle function, subsequent to genetic mutations, such as muscle dystrophy”, comments Dr. Hiroyasu Yamamoto, the first author on the study. Prof. Auwerx, however, points to another perhaps more important indication, muscle weakness also known as frailty, the prime cause of falling in the elderly. “We are actively screening to identify compounds and drugs that inhibit NCoR1 to treat these muscle disease” comments Auwerx.
These newly discovered mechanisms by which NCoR1 functions hence lays the foundation for a new therapeutic avenues that one day may be beneficial in treating diseases, ranging from muscle weakness and frailty to obesity and diabetes.

Hiroyasu Yamamoto, et al., Cell, Volume 147, Issue 4, 827-839, 10.1016/j.cell.2011.10.017 (2011)

Pingping Li et al., Cell, Volume 147, Issue 4, 815-826, 11, 10.1016/j.cell.2011.09.050 (2011)

Nature | Research Highlights - Genetic switch for big muscles. Nature 479, 271 (17 November 2011) doi:10.1038/479271c