9- and 13-HODE regulate fatty acid binding protein-4 in human macrophages, but does not involve HODE/GPR132 axis in PPAR-gamma regulation of FABP4

Vangaveti, Venkat, Shashidhar, Venkatesh, Collier, Fiona, Hodge, Jason, Rush, Catherine, Malabu, Usman, Baune, Bernhard, and Kennedy, Richard (2018) 9- and 13-HODE regulate fatty acid binding protein-4 in human macrophages, but does not involve HODE/GPR132 axis in PPAR-gamma regulation of FABP4. Therapeutic Advances in Endocrinology and Metabolism, 9 (5). pp. 137-150.

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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-gamma 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-gamma mediated induction of FABP4 by HODEs.

Item ID: 53787
Item Type: Article (Refereed Research - C1)
Keywords: FABP4, HODEs, macrophages
ISSN: 2042-0196
Funders: Townsville Hospital Private Practice Trust Fund, James Cook University
Date Deposited: 30 May 2018 07:34
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110306 Endocrinology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920104 Diabetes @ 100%
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