Cells control energy metabolism via hedgehog signalling pathway

Scientists have discovered a novel diabetes and obesity therapy, and potential cause of major side effects from hedgehog inhibitors used as a cancer treatment.

Cancer, diabetes, and excess body weight have one thing in common: they alter cellular metabolism. Scientists from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg and the Medical University of Vienna together with an international research team have jointly resolved a new molecular circuit controlling cellular metabolism.

The previously unknown signalling pathway, acting downstream of the hedgehog protein enables muscle cells and brown fat cells to absorb sugars without relying on insulin. Substances that selectively activate the signalling pathway could thus be utilised in the treatment of diabetes and obesity. With their results, the researchers are also able to explain why various new anti-cancer agents have induced mysterious pronounced side effects in the clinics.

Hedgehog was initially identified as an important protein for embryonic development across various organisms. Without hedgehog, the physiological partitions of the embryo become indistinct.

However, hedgehog also influences replication, migration and specialisation of cells – that is, the processes that also play a role in carcinogenesis. Mutation of genes also occurs concomitantly in various types of cancer, such as pancreatic, gastric or intestinal carcinomas. Above and beyond this, hedgehog inhibits the formation of ''bad'' white adipose tissue. Brown or ''good'' fat that serves to control body temperature, however, remains unaffected.

Hedgehog is therefore a very promising target for medications that fight cancer, diabetes and excess body weight. The US Food and Drug Administration (FDA) approved the first hedgehog inhibitor, Vismodegib, for treatment of cancer this year.