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Cell Metab. 2017 Feb 7;25(2):448-462. doi: 10.1016/j.cmet.2016.12.008. Epub 2017 Jan 5.

Adipocyte Dynamics and Reversible Metabolic Syndrome in Mice with an Inducible Adipocyte-Specific Deletion of the Insulin Receptor.

Author information

  • 1Section of Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • 2Section of Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Division of Endocrinology and Metabolism, Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
  • 3Section of Islet Cell & Regenerative Biology, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • 4Section of Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA. Electronic address: c.ronald.kahn@joslin.harvard.edu.

Abstract

Insulin and IGF1 signaling are important for adipose tissue development and function; however, their role in mature adipocytes is unclear. Mice with a tamoxifen-inducible knockout of insulin and/or IGF1 receptors (IR/IGF1R) demonstrate a rapid loss of white and brown fat due to increased lipolysis and adipocyte apoptosis. This results in insulin resistance, glucose intolerance, hepatosteatosis, islet hyperplasia with hyperinsulinemia, and cold intolerance. This phenotype, however, resolves over 10-30 days due to a proliferation of preadipocytes and rapid regeneration of both brown and white adipocytes as identified by mTmG lineage tracing. This cycle can be repeated with a second round of receptor inactivation. Leptin administration prior to tamoxifen treatment blocks development of the metabolic syndrome without affecting adipocyte loss or regeneration. Thus, IR is critical in adipocyte maintenance, and this loss of adipose tissue stimulates regeneration of brown/white fat and reversal of metabolic syndrome associated with fat loss.

KEYWORDS:

adipocyte regeneration; adipogenesis; brown adipocyte; fatty liver; insulin action; insulin receptor knockout; insulin resistance; leptin; lineage tracing; β cell proliferation

PMID:
28065828
PMCID:
PMC5304432
[Available on 2018-02-07]
DOI:
10.1016/j.cmet.2016.12.008
[PubMed - in process]
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