title: Hedgehog signalling in myeloid cells impacts on body weight, adipose tissue inflammation and glucose metabolism.
abstract: Recently, hedgehog (Hh) was identified as a crucial player in adipose tissue development and energy expenditure. Therefore, we tested whether Hh ligands are regulated in obesity. Further, we aimed at identifying potential target cells of Hh signalling and studied the functional impact of Hh signalling on adipose tissue inflammation and glucose metabolism.
  
  
  
  Hh ligands and receptors were analysed in adipose tissue or serum from lean and obese mice as well as in humans. To study the impact on adipose tissue inflammation and glucose metabolism, Hh signalling was specifically blocked in myeloid cells using a conditional knockout approach (Lys-Smo-/-).
  
  
  
  Desert Hh (DHH) and Indian Hh (IHH) are local Hh ligands, whereas Sonic Hh is not expressed in adipose tissue from mice or humans. In mice, obesity leads to a preferential upregulation of Hh ligands (Dhh) and signalling components (Ptch1, Smo and Gli1) in subcutaneous adipose tissue. Further, adipose tissue macrophages are Hh target cells owing to the expression of Hh receptors, such as Patched1 and 2. Conditional knockout of Smo (which encodes Smoothened, a mandatory Hh signalling component) in myeloid cells increases body weight and adipose tissue inflammation and attenuates glucose tolerance, suggesting an anti-inflammatory effect of Hh signalling. In humans, adipose tissue expression of DHH and serum IHH decrease with obesity and type 2 diabetes, which might be explained by the intake of metformin. Interestingly, metformin reduced Dhh and Ihh expression in mouse adipose tissue explants.
  
  
  
  Hh signalling in myeloid cells affects adipose tissue inflammation and glucose metabolism and may be a potential target to treat type 2 diabetes.
authors.affiliation: Institute of Anatomy, Leipzig University, Oststrasse 25, D-04317, Leipzig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Braune
authors.affiliation: Institute of Anatomy, Leipzig University, Oststrasse 25, D-04317, Leipzig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Weyer
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, Leipzig University, Leipzig, Germany.
authors.forename: Madlen
authors.initials: M
authors.lastname: Matz-Soja
authors.affiliation: Institute of Anatomy, Leipzig University, Oststrasse 25, D-04317, Leipzig, Germany.
authors.forename: Constance
authors.initials: C
authors.lastname: Hobusch
authors.affiliation: German Center of Diabetes Research (DZD), Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kern
authors.affiliation: IFB Adiposity Disease, Core Unit, Leipzig University, Leipzig, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kunath
authors.affiliation: IFB Adiposity Disease, Core Unit, Leipzig University, Leipzig, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
authors.affiliation: Department of Medicine, Leipzig University, Leipzig, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Kralisch
authors.affiliation: Department of Medicine, Leipzig University, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, Leipzig University, Leipzig, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Gebhardt
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, USA.
authors.forename: Yana
authors.initials: Y
authors.lastname: Zavros
authors.affiliation: Institute of Anatomy, Leipzig University, Oststrasse 25, D-04317, Leipzig, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.affiliation: Institute of Anatomy, Leipzig University, Oststrasse 25, D-04317, Leipzig, Germany. martin.gericke@medizin.uni-leipzig.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Gericke
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D053823:Hedgehog Proteins; D005947:Glucose
keywords: Adipose tissue; Diabetes; Glucose tolerance; Hedgehog; Inflammation; Macrophages; Obesity; Smo