Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Carl Owen, Alicja Czopek, Abdelali Agouni, Louise Grant, Robert Judson, Emma K Lees, George D McIlroy, Olga Göransson, Andy Welch, Kendra K Bence, Barbara B Kahn, Benjamin G Neel, Nimesh Mody, Mirela Delibegovic

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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 Crerecombinase 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 hypoxiainduced factor-1-alpha (Hif-1a) 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.
Original languageEnglish
Article numbere32700
Number of pages15
JournalPloS ONE
Volume7
Issue number2
Early online date27 Feb 2012
DOIs
Publication statusPublished - 28 Feb 2012

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