A-FABP in Metabolic Diseases and the Therapeutic Implications: An Update

Abstract

Adipocyte fatty acid-binding protein (A-FABP), which is also known as ap2 or FABP4, is a fatty acid chaperone that has been further defined as a fat-derived hormone. It regulates lipid homeostasis and is a key mediator of inflammation. Circulating levels of A-FABP are closely associated with metabolic syndrome and cardiometabolic diseases with imminent diagnostic and prognostic significance. Numerous animal studies have elucidated the potential underlying mechanisms involving A-FABP in these diseases. Recent studies demonstrated its physiological role in the regulation of adaptive thermogenesis and its pathological roles in ischemic stroke and liver fibrosis. Due to its implication in various diseases, A-FABP has become a promising target for the development of small molecule inhibitors and neutralizing antibodies for disease treatment. This review summarizes the clinical and animal findings of A-FABP in the pathogenesis of cardio-metabolic diseases in recent years. The underlying mechanism and its therapeutic implications are also highlighted.

High Serum FABP4 Levels are Negatively Associated with the Reversion from Prediabetes to Normal Glucose Tolerance: A 2-Year Retrospective Cohort Community Study

“…Due to the implications of FABP4 in various diseases, FABP4 has become a promising target for the treatment of metabolic dysfunction. 31,32 Our results suggested that FABP4 inhibitors, if developed in the future, might be able not only to treat diabetes but also to prevent it.…”

Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

“…There is strong evidence correlating elevated AFABP with IR and adipose tissue lipolysis in obesity and metabolic syndrome [ 33 ]. Interestingly, a recent review pointed out that AFABP as a metabolic/functional marker regulating macrophage functions likely having a determining role in pathophysiology [ 69 ].…”

Targeting Fatty Acid-Binding Protein 4 Improves Pathologic Features of Aortic Stenosis

“…Fatty acid-binding protein (FABP) 4 is a long chain fatty acid chaperone that plays a key role in intracellular lipid transport and homeostasis, regulating lipolysis in adipose tissue [ 11 ]. It is mainly expressed and secreted from adipocytes, but it can also be found in macrophages and endothelial cells.…”

“…It is mainly expressed and secreted from adipocytes, but it can also be found in macrophages and endothelial cells. Such increased expression leads to cholesterol ester accumulation, foam cell formation, and/or endothelial dysfunction [ 11 ]. The secreted form might act as an adipokine, targeting multiple organs and cell types [ 12 ].…”

“…The secreted form might act as an adipokine, targeting multiple organs and cell types [ 12 ]. FABP4 contributes to the development of a variety of pathological conditions associated with the metabolic syndrome cluster such as insulin resistance, obesity, hypertension, heart failure, and atherosclerosis [ 11 ]. Of special interest, ectopic expression of FABP4 in atherosclerotic plaques is due to its excessive production by macrophages that infiltrates within the lesion, being associated with greater local inflammation or plaque vulnerability [ 13 ].…”