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Hedgehog signalling pathway in adult liver: a major new player in hepatocyte metabolism and zonation

Abstract:

Metabolic Zonation, i.e. the heterogeneous distribution of different metabolic pathways in different zones of the lobules, forms the basis of proper function of the liver in metabolic homeostasis and its regulation. According to recent results, Metabolic Zonation is controlled by the Wnt/β-catenin signalling pathway. Here, we hypothesize that hedgehog signalling via Indian hedgehog ligands plays an equal share in this control although, up to now, hedgehog signalling is considered not to be active in healthy adult hepatocytes. We provide broad evidence taken mainly by analogy from other mature organs that hedgehog signalling in adult hepatocytes may particularly control liver lipid and cholesterol metabolism as well as certain aspects of hormone biosynthesis. Like Wnt/β-catenin signalling, it seems to act on a very low level forming a porto-central gradient in the lobules opposite to that of Wnt/β-catenin signalling with which it is interacting by mutual inhibition. Consequently, modulation of hedgehog signalling by endogenous and exogenous agents may considerably impact on liver lipid metabolism and beyond. If functioning improperly, it may possibly contribute to diseases like non-alcoholic fatty liver disease (NAFLD) and other diseases such as lipodystrophy.

23433827

Projects: Virtual Liver

Med. Hypotheses
Med. Hypotheses 80(5): 589-94
21st Feb 2013

Madlen Matz-Soja, Amalya Hovhannisyan, Rolf Gebhardt

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[Madlen Matz-Soja] [Amalya Hovhannisyan] [Rolf Gebhardt]

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Liver
Views: 1767
  • Created: 4th Feb 2014 at 08:09

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