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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 3

BMT experiments in FABP-deficient mice.

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BMT experiments in FABP-deficient mice.
(A) Experimental design of the B...
(A) Experimental design of the BMT studies using WT (Ap2+/+Mal1+/+) and FABP-deficient (Ap2–/–Mal1–/–) mice. The numbers in parentheses indicate the timing (week) of performed items. (B) Description and nomenclature for the groups of BMT mice. (C) Genotyping using DNA samples from blood and tail in BMT mice. The graphs on the right show the quantification for the percentages of WT and KO alleles in blood samples. Data are shown as mean ± SEM. (D) Genotyping using DNA samples from white adipose tissue (WAT), liver, and skeletal muscle (soleus) in BMT mice for the donor and recipient alleles. GTT, glucose tolerance test; ITT, insulin tolerance test; Met Cage, metabolic cage study; DEXA, dual energy x-ray absorptiometry; Clamp, hyperinsulinemic-euglycemic clamp study.

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