Lipid Chaperones and Metabolic Inflammation

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.