Z Gastroenterol 2020; 58(01): e34
DOI: 10.1055/s-0039-3402191
Poster Visit Session III Metabolism (incl. NAFLD): Friday, February 14, 2020, 4:40 pm – 5:25 pm, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

Hedgehog Signaling as a mediator between liver and adipose tissue

F Ott
1   Leipzig University, Rudolf-Schönheimer-Institute for Biochemistry, Leipzig, Germany
,
K Werner
1   Leipzig University, Rudolf-Schönheimer-Institute for Biochemistry, Leipzig, Germany
,
M Gericke
2   Institute of Anatomy and Cell Biology, MLU, Halle (Saale), Germany
,
R Gebhardt
1   Leipzig University, Rudolf-Schönheimer-Institute for Biochemistry, Leipzig, Germany
,
M Matz-Soja
1   Leipzig University, Rudolf-Schönheimer-Institute for Biochemistry, Leipzig, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

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Question:

In recent years it has become apparent that the morphogenic Hedgehog (Hh) pathway is not only active during embryonic development, but also in adult organs, controlling metabolism and maintaining homeostasis. The liver in particular as a metabolically active organ with many functions in energy homeostasis is of interest, especially since active Hh signaling could be detected in hepatocytes.

Crosstalk between the liver and tissues of the periphery such as the adipose tissue (AT) has long since been known. Prior experiments have revealed that inactivation of Hh in hepatocytes leads to morphogenic changes in several tissues, one of which is the AT. The mechanism and implications of such a Hh-dependent crosstalk between the tissues remain to be elucidated.

Methods:

Primary hepatocytes as well as the different types of AT – visceral (VAT), subcutaneous (SAT) and brown (BAT) – were isolated from two mouse strains with specific inactivation of Hh signaling in hepatocytes. Morphologic and biochemical characterization of AT by immunohistochemistry including analysis of adipocyte size as well as by molecular biological methods such as qPCR was performed.

Results:

Mice with an inactivation of Hh signaling in hepatocytes have a distinct phenotype in AT: an increase of all types of AT in both sexes as well as a changed distribution of cell size could be detected. Furthermore there are changes in the gene expression profile. Brown and beige adipocyte markers show increased expression, and lipid metabolism, in particular lipogenesis, seems to be affected in AT. Immunohistochemistry revealed UCP-1-positive cell clusters in VAT and SAT, indicating a browning effect.

Conclusions:

A hepatocyte-specific inactivation of Hh leads to phenotypic and metabolic changes in the AT of mice, resulting in the emergence of brown adipocytes in SAT and, more intensely, in VAT. Although the mechanism of Hh-mediated crosstalk between liver and AT remains elusive, the results reveal a novel and highly interesting aspect of how morphogenic pathways control metabolism through inter-organ communication.