Owen, C and Czopek, A and Agouni, A and Grant, L and Judson, R and Lees, EK and Mcilroy, GD and Goransson, O and Welch, A and Bence, KK and Kahn, BB and Neel, BG and Mody, N and Delibegovic, M (2012) Adipocyte-Specific Protein Tyrosine Phosphatase 1B Deletion Increases Lipogenesis, 1 Adipocyte Cell Size and is a Minor Regulator of Glucose Homeostasis. PLoS One, 7 (2).
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Abstract
Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of leptin and insulin signaling, is positively correlated with adiposity and contributes to insulin resistance. Global PTP1B deletion improves diet-induced obesity and glucose homeostasis via enhanced leptin signaling in the brain and increased insulin signaling in liver and muscle. However, the role of PTP1B in adipocytes is unclear, with studies demonstrating beneficial, detrimental or no effect(s) of adipose-PTP1B-deficiency on body mass and insulin resistance. To definitively establish the role of adipocyte-PTP1B in body mass regulation and glucose homeostasis,
adipocyte-specific-PTP1B knockout mice (adip-crePTP1B-/-) were generated using the adiponectin-promoter to drive Cre-recombinase expression. Chow-fed adip-crePTP1B-/- mice display enlarged adipocytes, despite having similar body weight/adiposity and glucose homeostasis compared to controls. High-fat diet (HFD)-fed adip-crePTP1B-/- mice display no differences in body weight/adiposity but exhibit larger adipocytes, increased circulating glucose and leptin levels, reduced leptin sensitivity and increased basal lipogenesis compared to controls. This is associated with decreased insulin receptor (IR) and Akt/PKB phosphorylation, increased lipogenic gene expression and increased hypoxia-induced factor-1-alpha (Hif-1α) expression. Adipocyte-specific PTP1B deletion does not beneficially manipulate signaling pathways regulating glucose homeostasis, lipid metabolism or adipokine secretion in adipocytes. Moreover, PTP1B does not appear to be the major negative regulator of the IR in adipocytes.
| Item Type: | Article |
|---|---|
| Additional Information and Comments: | © 2012 Owen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
| Faculty / Department: | Faculty of Human and Digital Sciences > School of Health and Sport Sciences |
| Depositing User: | Emma Lees |
| Date Deposited: | 04 Apr 2016 11:13 |
| Last Modified: | 14 Nov 2017 11:51 |
| URI: | https://hira.hope.ac.uk/id/eprint/1113 |
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