Journal article
Adipocyte Dynamics and Reversible Metabolic Syndrome in Mice with an Inducible Adipocyte-Specific Deletion of the Insulin Receptor
Cell metabolism, Vol.25(2), pp.448-462
02/07/2017
DOI: 10.1016/j.cmet.2016.12.008
PMCID: PMC5304432
PMID: 28065828
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.
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•Mature adipose tissue depends on insulin signaling for maintenance and survival•Acute loss of insulin signaling in fat results in a reversible metabolic syndrome•Fat loss stimulates preadipocyte proliferation and regeneration of white/brown fat•Inducible lipodystrophy stimulates rapid proliferation of pancreatic β cells
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.
Details
- Title: Subtitle
- Adipocyte Dynamics and Reversible Metabolic Syndrome in Mice with an Inducible Adipocyte-Specific Deletion of the Insulin Receptor
- Creators
- Masaji Sakaguchi - Joslin Diabetes CenterShiho Fujisaka - Joslin Diabetes CenterWeikang Cai - Joslin Diabetes CenterJonathon N. Winnay - Joslin Diabetes CenterMasahiro Konishi - Joslin Diabetes CenterBrian T. O'Neill - Joslin Diabetes CenterMengyao Li - Joslin Diabetes CenterRubén García-Martín - Joslin Diabetes CenterHirokazu Takahashi - Joslin Diabetes CenterJiang Hu - Joslin Diabetes CenterRohit N. Kulkarni - Joslin Diabetes CenterC. Ronald Kahn - Joslin Diabetes Center
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.25(2), pp.448-462
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cmet.2016.12.008
- PMID
- 28065828
- PMCID
- PMC5304432
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: R37DK031036, R01DK082659, R01DK67536, R01DK103215; name: Diabetes Endocrinology Research Center, award: P30DK034834; name: Mary K. Iacocca Professorship; DOI: 10.13039/501100007664, name: Manpei Suzuki Diabetes Foundation, award: MSDF2011-88; DOI: 10.13039/501100001691, name: Japan Society for the Promotion of Science, award: JP2014-780
- Language
- English
- Date published
- 02/07/2017
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359676602771
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