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

Citation
Sakaguchi, M., et al. “Adipocyte Dynamics And Reversible Metabolic Syndrome In Mice With An Inducible Adipocyte-Specific Deletion Of The Insulin Receptor.”. Cell Metabolism, pp. 448-462.
Center Joslin Diabetes Center
Author Masaji Sakaguchi, Shiho Fujisaka, Weikang Cai, Jonathon N Winnay, Masahiro Konishi, Brian T O'Neill, Mengyao Li, Ruben Garcia-Martin, Hirokazu Takahashi, Jiang Hu, Rohit N Kulkarni, Ronald Kahn
Keywords adipocyte regeneration, adipogenesis, brown adipocyte, fatty liver, Insulin action, insulin receptor knockout, Insulin resistance, leptin, LINEAGE TRACING, β cell proliferation
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.

Year of Publication
2017
Journal
Cell metabolism
Volume
25
Issue
2
Number of Pages
448-462
Date Published
12/2017
ISSN Number
1932-7420
DOI
10.1016/j.cmet.2016.12.008
Alternate Journal
Cell Metab.
PMID
28065828
PMCID
PMC5304432
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