The Hedgehog signaling pathway regulates many processes during embryogenesis and
the homeostasis of adult organs. Recent data suggest that central metabolic processes and signaling
cascades in the liver are controlled by the Hedgehog pathway and that changes in hepatic Hedgehog
activity also affect peripheral tissues, such as the reproductive organs in females. Here, we show that
hepatocyte-specific deletion of the Hedgehog pathway is associated with the dramatic expansion of
adipose tissue in mice, the overall phenotype of which does not correspond to the classical outcome of
insulin resistance-associated diabetes type 2 obesity. Rather, we show that alterations in the Hedgehog
signaling pathway in the liver lead to a metabolic phenotype that is resembling metabolically healthy
obesity. Mechanistically, we identified an indirect influence on the hepatic secretion of the fibroblast
growth factor 21, which is regulated by a series of signaling cascades that are directly transcriptionally
linked to the activity of the Hedgehog transcription factor GLI1. The results of this study impressively
show that the metabolic balance of the entire organism is maintained via the activity of morphogenic
signaling pathways, such as the Hedgehog cascade. Obviously, several pathways are orchestrated to
facilitate liver metabolic status to peripheral organs, such as adipose tissue.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87349 |
| Date | 09 October 2023 |
| Creators | Ott, Fritzi, Körner, Christiane, Werner, Kim, Gericke, Martin, Liebscher, Ines, Lobsien, Donald, Radrezza, Silvia, Shevchenko, Andrej, Hofmann, Ute, Kratzsch, Jürgen, Gebhardt, Rolf, Berg, Thomas, Matz-Soja, Madlen |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1680, 10.3390/cells11101680 |
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