10027/21166
Guifen Qiang
Guifen
Qiang
Hyerim W. Kong
Hyerim W.
Kong
Shanshan Xu
Shanshan
Xu
Hoai A. Phan
Hoai A.
Phan
Sebastian D. Parlee
Sebastian D.
Parlee
Aaron A. Burr
Aaron A.
Burr
Victoria Gil
Victoria
Gil
Jingbo Pang
Jingbo
Pang
Amy Hughes
Amy
Hughes
Xuejiang Gu
Xuejiang
Gu
Giamila Fantuzzi
Giamila
Fantuzzi
Ormond A. MacDougald
Ormond A.
MacDougald
Chongwee Liew
Chongwee
Liew
Lipodystrophy and severe metabolic dysfunction
in mice with adipose tissue-specific insulin
receptor ablation
University of Illinois at Chicago
2016
Brown adipose tissue
Insulin signaling
Lipodystrophy
Marrow adipose tissue
White adipose tissue
2016-09-14 00:00:00
Journal contribution
https://indigo.uic.edu/articles/journal_contribution/Lipodystrophy_and_severe_metabolic_dysfunction_in_mice_with_adipose_tissue-specific_insulin_receptor_ablation/10778486
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.