Venkat Vangaveti1, Venkatesh Shashidhar2, Fiona Collier3, Jason Hodge3, Catherine Rush4, Usman Malabu2, Bernhard Baune5, Richard Lee Kennedy3. 1. Room 114, Building 47, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia 4814, Australia. 2. College of Medicine and Dentistry, James Cook University, Queensland, Australia. 3. School of Medicine, Deakin University, Victoria, Australia. 4. College of Public Health, Medical & Vet Sciences, James Cook University, Queensland, Australia. 5. Department of Psychiatry, University of Adelaide, South Australia.
Abstract
BACKGROUND: Both activation of monocytes and increased serum fatty acid binding protein-4 (FABP4) occur in diabetes and are associated with increased atherosclerosis. The oxidized lipid, 9-hydroxyoctadecadienoic acid (9-HODE) increases FABP4 in macrophages, and is a ligand for G protein-coupled receptor 132 (GPR132). We investigated the involvement of GPR132 in mediating the 9-, 13-HODE stimulation of FABP4 secretion, and whether GPR132 expression is increased in monocytes from patients with type 2 diabetes. METHODS: The effects of siRNA silencing of GPR132 gene and of the PPAR-γ antagonist T0070907 were studied in THP-1 cells. Serum levels of FABP4 and other adipokines were measured in patients with diabetes, and monocyte subpopulations were analyzed using flow cytometry. GPR132 mRNA was quantified in isolated CD14+ cells. RESULTS: 9-HODE and 13-HODE increased FABP4 expression in THP-1 monocytes and macrophages, and also increased GPR132 expression. Silencing of GPR132 did not influence the increase in FABP4 with 9-HODE, 13-HODE, or rosiglitazone (ROSI). By contrast, T0070907 inhibited the effect of all three ligands on FABP4 expression. Diabetic subjects had increased serum FABP4, and activated monocytes. They also expressed higher levels of GPR132 mRNA in CD14+ cells. CONCLUSIONS: We conclude that GPR132 is an independent monocyte activation marker in diabetes, but does not contribute to PPAR-γ-mediated induction of FABP4 by HODEs.
BACKGROUND: Both activation of monocytes and increased serum fatty acid binding protein-4 (FABP4) occur in diabetes and are associated with increased atherosclerosis. The oxidized lipid, 9-hydroxyoctadecadienoic acid (9-HODE) increases FABP4 in macrophages, and is a ligand for G protein-coupled receptor 132 (GPR132). We investigated the involvement of GPR132 in mediating the 9-, 13-HODE stimulation of FABP4 secretion, and whether GPR132 expression is increased in monocytes from patients with type 2 diabetes. METHODS: The effects of siRNA silencing of GPR132 gene and of the PPAR-γ antagonist T0070907 were studied in THP-1 cells. Serum levels of FABP4 and other adipokines were measured in patients with diabetes, and monocyte subpopulations were analyzed using flow cytometry. GPR132 mRNA was quantified in isolated CD14+ cells. RESULTS: 9-HODE and 13-HODE increased FABP4 expression in THP-1 monocytes and macrophages, and also increased GPR132 expression. Silencing of GPR132 did not influence the increase in FABP4 with 9-HODE, 13-HODE, or rosiglitazone (ROSI). By contrast, T0070907 inhibited the effect of all three ligands on FABP4 expression. Diabetic subjects had increased serum FABP4, and activated monocytes. They also expressed higher levels of GPR132 mRNA in CD14+ cells. CONCLUSIONS: We conclude that GPR132 is an independent monocyte activation marker in diabetes, but does not contribute to PPAR-γ-mediated induction of FABP4 by HODEs.
Authors: Jade K A Hampel; Leon M Brownrigg; Dayalan Vignarajah; Kevin D Croft; Arun M Dharmarajan; Jacqueline M Bentel; Ian B Puddey; Bu B Yeap Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2006-05-02 Impact factor: 4.006
Authors: Venkat N Vangaveti; Venkatesh M Shashidhar; Catherine Rush; Usman H Malabu; Roy R Rasalam; Fiona Collier; Bernhard T Baune; Richard L Kennedy Journal: Lipids Date: 2014-10-21 Impact factor: 1.880