Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation

Guifen Qiang, Hyerim Whang Kong, Shanshan Xu, Hoai An Pham, Sebastian D. Parlee, Aaron A. Burr, Victoria Gil, Jingbo Pang, Amy Hughes, Xuejiang Gu, Giamila Fantuzzi, Ormond A. MacDougald, Chong Wee Liew

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

LanguageEnglish
Pages480-490
Number of pages11
JournalMolecular Metabolism
Volume5
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • Brown adipose tissue
  • Insulin signaling
  • Lipodystrophy
  • Marrow adipose tissue
  • White adipose tissue

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Qiang, G., Whang Kong, H., Xu, S., Pham, H. A., Parlee, S. D., Burr, A. A., ... Liew, C. W. (2016). Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation. Molecular Metabolism, 5(7), 480-490. https://doi.org/10.1016/j.molmet.2016.05.005
Qiang, Guifen ; Whang Kong, Hyerim ; Xu, Shanshan ; Pham, Hoai An ; Parlee, Sebastian D. ; Burr, Aaron A. ; Gil, Victoria ; Pang, Jingbo ; Hughes, Amy ; Gu, Xuejiang ; Fantuzzi, Giamila ; MacDougald, Ormond A. ; Liew, Chong Wee. / Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation. In: Molecular Metabolism. 2016 ; Vol. 5, No. 7. pp. 480-490.
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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.",
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Qiang, G, Whang Kong, H, Xu, S, Pham, HA, Parlee, SD, Burr, AA, Gil, V, Pang, J, Hughes, A, Gu, X, Fantuzzi, G, MacDougald, OA & Liew, CW 2016, 'Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation', Molecular Metabolism, vol. 5, no. 7, pp. 480-490. https://doi.org/10.1016/j.molmet.2016.05.005

Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation. / Qiang, Guifen; Whang Kong, Hyerim; Xu, Shanshan; Pham, Hoai An; Parlee, Sebastian D.; Burr, Aaron A.; Gil, Victoria; Pang, Jingbo; Hughes, Amy; Gu, Xuejiang; Fantuzzi, Giamila; MacDougald, Ormond A.; Liew, Chong Wee.

In: Molecular Metabolism, Vol. 5, No. 7, 01.07.2016, p. 480-490.

Research output: Contribution to journalArticle

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T1 - Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation

AU - Qiang, Guifen

AU - Whang Kong, Hyerim

AU - Xu, Shanshan

AU - Pham, Hoai An

AU - Parlee, Sebastian D.

AU - Burr, Aaron A.

AU - Gil, Victoria

AU - Pang, Jingbo

AU - Hughes, Amy

AU - Gu, Xuejiang

AU - Fantuzzi, Giamila

AU - MacDougald, Ormond A.

AU - Liew, Chong Wee

PY - 2016/7/1

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N2 - 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.

AB - 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.

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