Table 1.
Features of FABP4 and FABP5 in metaflammation and related diseases.
| Expression | Regulation and function | Connection to diseases | Reference | |
|---|---|---|---|---|
| FABP4 | Adipocyte | Induction by fatty acids, PPARγ agonists, dexamethazone, and insulin | [23–27] | |
| Lipolysis (interaction with HSL) | [28–30] | |||
| Regulation of insulin secretion during lipolysis | [29] | |||
| Fatty acid sensor (interaction with JAK2) | [31] | |||
| Regulation of lipid metabolism and differentiation (interaction with PTEN) | [32] | |||
| Protection from insulin resistance and diabetes in deficient mice | Insulin resistance, diabetes | [14, 15, 18, 19, 21] | ||
| Protection from insulin resistance and diabetes by a FABP4 inhibitor | Insulin resistance, diabetes | [33] | ||
| Macrophage | Induction by PMA, LPS, PPARγ agonists, ox-LDL, and AGE/RAGE | [11, 34–38] | ||
| Reduction by atorvastatin and metformin | [39, 40] | |||
| Activation of IKK-NF-κB pathway | [41] | |||
| Activation of JNK-AP-1 pathway | [42] | |||
| Inhibition of PPARγ-LXRα-ABCA1 pathway | [41] | |||
| FOXO1-mediated transcription | [40] | |||
| Association with ER stress | [22] | |||
| Protection from insulin resistance and diabetes in double-deficient mice* | Insulin resistance, diabetes | [21] | ||
| Protection from atherosclerosis in deficient mice | Atherosclerosis | [11, 16, 20] | ||
| Protection from insulin resistance and atherosclerosis by a FABP4 inhibitor | Insulin resistance, atherosclerosis | [33] | ||
| Dendritic cell | Activation of IKK-NF-κB pathway | [12] | ||
| T-cell priming | [12] | |||
| Endothelial cell | Expression in capillary and small vein but not in artery | [43] | ||
| Regulation by VEGF-A/VEGFR2 and bFGF | [43] | |||
| Induction in regenerated endothelial cells after balloon denudation of artery | [44] | |||
| Induction by intermittent hypoxia | [45] | |||
| FOXO1-mediated transcription inhibited by angiopoietin-1 | [46] | |||
| Expression in aortic endothelium of old ApoE-deficient mice | [47] | |||
| Improvement of dysfunction in aortic endothelium by a FABP4 inhibitor | Endothelial dysfunction | [47] | ||
| Association with oxidative stress and activation of NF-κB and P53 pathways | Cellular senescence | [48, 49] | ||
| Bronchial epithelial cell | Induction by Th2 cytokines IL-4 and IL-13 | [13] | ||
| Suppression by Th1 cytokine interferon γ | [13] | |||
| Noninduction by PPARγ agonists | [13] | |||
| Protection from asthma in deficient mice | Asthma | [13] | ||
| Lung | Detection in lung lavage cells obtained from patients | Bronchopulmonary dysplasia | [50] | |
| Detection in lung lavage cells obtained from patients | Sarcoidosis | [51] | ||
| Ovary | Expression in granulosa cells inside atretic antral follicles | [52] | ||
| Association with FABP4 gene polymorphisms | Polycystic ovary syndrome | [53] | ||
| Spleen | Induction by dexamethazone | [54] | ||
| T cell | Induction by dexamethazone | [54] | ||
| Keratinocyte | Induction in PTEN-deficient keratinocytes | [55] | ||
| Tumor | Detection in tumor | Lipoblastoma, liposarcoma | [56] | |
| Detection in tumor | Urothelial carcinoma | [57] | ||
| FABP5 | Adipocyte | Lipolysis | [58] | |
| Protection from insulin resistance and diabetes in deficient mice | Insulin resistance, diabetes | [17–19, 21] | ||
| Induction of insulin resistance in adipose-specific transgenic mice | Insulin resistance, diabetes | [17] | ||
| Macrophage | Regulation by TLR agonists: LPS (TLR4) and zymosan (TLR2) | [59] | ||
| Induction of inflammatory genes, COX2 and IL-6 | [60] | |||
| Protection from insulin resistance and diabetes in double-deficient mice* | Insulin resistance, diabetes | [21] | ||
| Protection from atherosclerosis in deficient mice | Atherosclerosis | [20, 60] | ||
| Liver | Induction by a high-cholesterol diet feeding in LDL-receptor-deficient mice | [61] | ||
| Others | Expression in skin, dendritic cell, tongue, mammary gland, brain, intestine, kidney, lung, heart, skeletal muscle, testis, retina, lens, and spleen | [7] |
ABCA1: ATP-binding cassette A1; AGE: advanced glycation end products; AP-1: activating protein-1; ApoE: apolipoprotein E; bFGF: basic fibroblast growth factor; COX2: cyclooxygenase-2; ER: endoplasmic reticulum; FOXO1: forkhead box protein O1; HSL: hormone-sensitive lipase; IKK: inhibitor of nuclear kappa B kinase; IL: interleukin; JAK2: Janus kinase 2; JNK: c-Jun N-terminal kinase; LDL: low-density lipoprotein; LPS: lipopolysaccharide; LXR: liver X receptor; NF-κB: nuclear factor-kappa B; ox-LDL: oxidized LDL; PMA: phorbol 12-myristate 13-acetate; PPAR: peroxisome proliferator-activated receptor; PTEN: phosphatase and tensin homolog on chromosome 10; RAGE: receptor for AGE; TLR: Toll-like receptor; VEGF-A: vascular endothelial growth factor-A; VEGFR2: VEGF-receptor-2.
*FABP4−/−FABP5−/− mice.