Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice.
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.
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Masato
M
Furuhashi
Raquel
R
Fucho
Cem Z
CZ
Görgün
Gürol
G
Tuncman
Haiming
H
Cao
Gökhan S
GS
Hotamisligil
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002450:Cell Communication / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009765:Obesity / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C493411:Fabp4 protein, mouse; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose