期刊
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
卷 26, 期 3, 页码 216-232出版社
JAPAN ATHEROSCLEROSIS SOC
DOI: 10.5551/jat.48710
关键词
Adipocyte; Macrophage; Endothelium; Atherosclerosis; Insulin resistance; Adipokine; aP2; A-FABP; Mal1; E-FABP
资金
- JSPS KAKENHI
- MEXT Translational Research Network Program
- Uehara Memorial Foundation
- SENSHIN Medical Research Foundation
- Japan Diabetes Foundation
- Takeda Medical Research Foundation
- Ono Medical Research Foundation
- Takeda Science Foundation
- Akiyama Life Science Foundation
- Yamaguchi Endocrine Research Foundation
- Naito Foundation Natural Science Scholarship
- Suhara Memorial Foundation
- Kondou Kinen Medical Foundation
- Terumo Foundation for Life Science and Arts
- Japan Atherosclerosis Society
Fatty acid-binding proteins (FABPs), a family of lipid chaperones, contribute to systemic metabolic regulation via several lipid signaling pathways. Fatty acid-binding protein 4 (FABP4), known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays important roles in the development of insulin resistance and atherosclerosis in relation to metabolically driven low-grade and chronic inflammation, referred to as 'metaflammation'. FABP4 is secreted from adipocytes in a non-classical pathway associated with lipolysis and acts as an adipokine for the development of insulin resistance and atherosclerosis. Circulating FABP4 levels are associated with several aspects of metabolic syndrome and cardiovascular disease. Ectopic expression and function of FABP4 in cells and tissues are also related to the pathogenesis of several diseases. Pharmacological modification of FABP4 function by specific inhibitors, neutralizing antibodies or antagonists of unidentified receptors would be novel therapeutic strategies for several diseases, including obesity, diabetes mellitus, atherosclerosis and cardiovascular disease. Significant roles of FABP4 as a lipid chaperone in physiological and pathophysiological conditions and the possibility of FABP4 being a therapeutic target for metabolic and cardiovascular diseases are discussed in this review.
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