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Adipocyte insulin receptor activity maintains adipose tissue mass and lifespan.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2016 Aug 05; Vol. 476 (4), pp. 487-492. Date of Electronic Publication: 2016 May 28. - Publication Year :
- 2016
-
Abstract
- Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion. Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase. Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis. These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan.<br /> (Copyright © 2016. Published by Elsevier Inc.)
- Subjects :
- Adipose Tissue anatomy & histology
Adipose Tissue metabolism
Aging metabolism
Animals
Blood Glucose metabolism
Diabetes Mellitus, Type 2 etiology
Diabetes Mellitus, Type 2 metabolism
Diabetes Mellitus, Type 2 pathology
Diet, High-Fat adverse effects
Female
Insulin Resistance physiology
Longevity physiology
Male
Mice
Mice, Knockout
Receptor, Insulin deficiency
Receptor, Insulin genetics
Signal Transduction
Adipocytes metabolism
Receptor, Insulin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 476
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 27246738
- Full Text :
- https://doi.org/10.1016/j.bbrc.2016.05.151