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Adipocyte/macrophage fatty acid–binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice
Masato Furuhashi, … , Haiming Cao, Gökhan S. Hotamisligil
Masato Furuhashi, … , Haiming Cao, Gökhan S. Hotamisligil
Published June 12, 2008
Citation Information: J Clin Invest. 2008;118(7):2640-2650. https://doi.org/10.1172/JCI34750.
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Research Article Metabolism Article has an altmetric score of 1

Adipocyte/macrophage fatty acid–binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice

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Abstract

Adipose tissue inflammation is a characteristic of obesity. However, the mechanisms that regulate this inflammatory response and link adipose inflammation to systemic metabolic consequences are not fully understood. In this study, we have taken advantage of the highly restricted coexpression of adipocyte/macrophage fatty acid–binding proteins (FABPs) aP2 (FABP4) and mal1 (FABP5) to examine the contribution of these lipid chaperones in macrophages and adipocytes to local and systemic inflammation and metabolic homeostasis in mice. Deletion of FABPs in adipocytes resulted in reduced expression of inflammatory cytokines in macrophages, whereas the same deletion in macrophages led to enhanced insulin signaling and glucose uptake in adipocytes. Using radiation chimerism through bone marrow transplantation, we generated mice with FABP deficiency in bone marrow and stroma-derived elements in vivo and studied the impact of each cellular target on local and systemic insulin action and glucose metabolism in dietary obesity. The results of these experiments indicated that neither macrophages nor adipocytes individually could account for the total impact of FABPs on systemic metabolism and suggest that interactions between these 2 cell types, particularly in adipose tissue, are critical for the inflammatory basis of metabolic deterioration.

Authors

Masato Furuhashi, Raquel Fucho, Cem Z. Görgün, Gürol Tuncman, Haiming Cao, Gökhan S. Hotamisligil

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Figure 2

Adipocyte and SV fractions in BMT (GFP-Tg→WT) mice.

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Adipocyte and SV fractions in BMT (GFP-Tg→WT) mice.
GFP-labeled donor ce...
GFP-labeled donor cells were used to track the destiny of bone marrow–derived cells. (A) Confirmation of the adipocyte (Ad) and SV fractions from WT, GFP-transgenic (GFP-Tg), and BMT (GFP-Tg→WT) mice by differential expression of adiponectin as an adipocyte and Pecam1 as a non-adipocyte SV marker. Data are shown as mean ± SEM. (B) Detection of Gfp mRNA by PCR in the same fractions shown in A. (C) Detection of GFP protein by Western blotting in the same fractions. Perilipin and PECAM-1 were controls of the Ad and SV fractions, respectively. (D) Fluorescence microscopic analysis of the adipose tissue fractions. In the adipocyte fraction, images were taken in both the centrifuged fat pad after digestion or in floating fat cells in DMEM with 10% cosmic calf serum (magnification, ×200). In the SV fraction, cells were observed at both the low and high magnifications (LM, ×100; and HM, ×400).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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