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

Publication date: Available online 5 January 2017
Source:Cell Metabolism
Author(s): Masaji Sakaguchi, Shiho Fujisaka, Weikang Cai, Jonathon N. Winnay, Masahiro Konishi, Brian T. O'Neill, Mengyao Li, Rubén García-Martín, Hirokazu Takahashi, Jiang Hu, Rohit N. Kulkarni, C. Ronald Kahn
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.

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Teaser

Sakaguchi et al. show that insulin signaling is necessary for maintenance of white and brown adipocytes mice in adult mice. Adipose tissue loss is reversed by a marked increase in both white and brown preadipocyte proliferation, indicating the presence of an adipostatic sensor. Adipocyte regeneration is leptin independent.


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