title: Changes in morphology and function of adrenal cortex in mice fed a high-fat diet.
abstract: OBJECTIVE
  Obesity is a major risk factor for the development of type 2 diabetes and other debilitating diseases. Obesity and diabetes are intimately linked with altered levels of adrenal steroids. Elevated levels of these hormones induce insulin resistance and cause cardiovascular diseases. The mechanisms underlying obesity-related alterations in adrenal steroids are still not well understood. Here, we investigated how diet-induced obesity affects the morphology and function of the mouse adrenal cortex.
  
  
  METHODS
  We fed animals either a high-fat diet (HFD) or a normal diet (60% kcal from fat or 10% kcal from fat, respectively) for 18 weeks. We then assessed various aspects of adrenal gland morphology and function, as well as basal plasma concentrations of steroid hormones and ACTH.
  
  
  RESULTS
  We show that adrenal glands of mice fed a HFD release more corticosterone and aldosterone, resulting in higher plasma levels. This increase is driven by adrenal cortical hyperplasia, and by increased expression of multiple genes involved in steroidogenesis. We demonstrate that diet-induced obesity elevates Sonic hedgehog signaling in Gli1-positive progenitors, which populate the adrenal capsule and give rise to the steroidogenic cells of the adrenal cortex. Feeding animals with a HFD depletes Gli1-positive progenitors, as the adrenal cortex expands.
  
  
  CONCLUSIONS
  This work provides insight into how diet-induced obesity changes the biology of the adrenal gland. The association of these changes with increased Shh signaling suggests possible therapeutic strategies for obesity-related steroid hormone dysfunction.
authors.affiliation: 1] Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany [2] Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Swierczynska
authors.affiliation: 1] Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany [2] Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Mateska
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Peitzsch
authors.affiliation: Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Chavakis
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Eisenhofer
authors.affiliation: Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Lamounier-Zepter
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Eaton
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000473:pathology*; D000071676:Zinc Finger Protein GLI1
chemical_list: D000305:Adrenal Cortex Hormones; C498520:Gli1 protein, mouse; D006360:Heat-Shock Proteins; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C465570:Shh protein, mouse; D000071676:Zinc Finger Protein GLI1; D003345:Corticosterone