title: Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation.
abstract: OBJECTIVE
  Insulin signaling plays pivotal roles in the development and metabolism of many tissues and cell types. A previous study demonstrated that ablation of insulin receptor (IR) with aP2-Cre markedly reduced adipose tissues mass and protected mice from obesity. However, multiple studies have demonstrated widespread non-adipocyte recombination of floxed alleles in aP2-Cre mice. These findings underscore the need to re-evaluate the role of IR in adipocyte and systemic metabolism with a more adipose tissue-specific Cre mouse line.
  
  
  METHODS
  We generated and phenotyped a new adipose tissue-specific IR mouse model using the adipose tissue-specific Adipoq-Cre line.
  
  
  RESULTS
  Here we show that the Adipoq-Cre-mediated IR KO in mice leads to lipodystrophy and metabolic dysfunction, which is in stark contrast to the previous study. In contrast to white adipocytes, absence of insulin signaling does not affect development of marrow and brown adipocytes, but instead is required for lipid accumulation particularly for the marrow adipocytes. Lipodystrophic IR KO mice have profound insulin resistance, hyperglycemia, organomegaly, and impaired adipokine secretion.
  
  
  CONCLUSIONS
  Our results demonstrate differential roles for insulin signaling for white, brown, and marrow adipocyte development and metabolic regulation.
authors.affiliation: Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Guifen
authors.initials: G
authors.lastname: Qiang
authors.affiliation: Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Hyerim
authors.initials: H
authors.lastname: Whang Kong
authors.affiliation: Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Hoai An
authors.initials: HA
authors.lastname: Pham
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Sebastian D
authors.initials: SD
authors.lastname: Parlee
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Burr
authors.affiliation: Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Gil
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Pang
authors.affiliation: Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Hughes
authors.affiliation: Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Giamila
authors.initials: G
authors.lastname: Fantuzzi
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Ormond A
authors.initials: OA
authors.lastname: MacDougald
authors.affiliation: Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: cwliew@uic.edu.
authors.forename: Chong Wee
authors.initials: CW
authors.lastname: Liew
keywords: Brown adipose tissue; Insulin signaling; Lipodystrophy; Marrow adipose tissue; White adipose tissue