Hedgehog Partial Agonism Drives Warburg-like Metabolism in Muscle and Brown Fat
Raffaele Teperino, Sabine Amann, Martina Bayer, Sean L. McGee, Andrea Loipetzberger, Timothy Connor, Carsten Jaeger, Bernd Kammerer, Lilli Winter, Gerhard Wiche, Kevin Dalgaard, Madhan Selvaraj, Michael Gaster, Robert S. Lee-Young, Mark A. Febbraio, Claude Knauf, Patrice D. Cani, Fritz Aberger, Josef M. Penninger, J. Andrew Pospisilik, and Harald Esterbauer

Abstract
Hedgehog signaling is a major regulator of cancer growth and cellular metabolism. Andrea Loipetzberger from the Aberger lab contributed to this pivotal study on a novel non-canonical Hedgehog signaling axis triggering insulin-independent glucose uptake and calcium influx. Intriguingly, both Hedgehog agonists and inhibitors can activate this novel signal axis. The finding of insulin-independent glucose uptake may provide a new therapeutic avenue for diabetes and obesity. By contrast, the same effect is likely to negatively affect cancer therapy, since glucose serves as major fuel for cancer growth. The findings on calcium influx explain the severe muscle cramps observed in up to 50 percent of patients treated with Hedgehog inhibitor drugs. The data call for a careful (re)design of therapeutic Hedgehog modulators for cancer and diabetes, taking into account the novel properties of non-canonical Hedgehog signaling discovered in this study.

The open access article can be found  here.

Reviewed by Johann Brandstetter