Fatty Acid-Binding Protein 4 (FABP4): Pathophysiological Insights and Potent Clinical Biomarker of Metabolic and Cardiovascular Diseases

Abstract

Over the past decade, evidences of an integration of metabolic and inflammatory pathways, referred to as metaflammation in several aspects of metabolic syndrome, have been accumulating. Fatty acid-binding protein 4 (FABP4), also known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays an important role in the development of insulin resistance and atherosclerosis in relation to metaflammation. Despite lack of a typical secretory signal peptide, FABP4 has been shown to be released from adipocytes in a non-classical pathway associated with lipolysis, possibly acting as an adipokine. Elevation of circulating FABP4 levels is associated with obesity, insulin resistance, diabetes mellitus, hypertension, cardiac dysfunction, atherosclerosis, and cardiovascular events. Furthermore, ectopic expression and function of FABP4 in several types of cells and tissues have been recently demonstrated. Here, we discuss both the significant role of FABP4 in pathophysiological insights and its usefulness as a biomarker of metabolic and cardiovascular diseases.

Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis

“…The long-chain monosaturated FFA oleate has been shown to be able to stimulate the proliferation of human breast cancer cells, with PI3K having a role in this process (Hsu et al, 2007;Hardy et al, 2005). Of note, FABP4 is an adipose tissue-secreted adipokine involved in the regulation of energy metabolism (Furuhashi et al, 2014), and plays an important role in FA uptake by cells (Wu et al, 2014). A recent study demonstrated that exogenous FABP4 can positively regulate cancer cell proliferation through the activation of PI3K-AKT and MAPK-ERK pathways in breast cancer cells (Guaita-Esteruelas et al, 2016).…”

Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

“…Possible mechanisms of reduced FABP4 concentration caused by sitagliptin. FABP4 is secreted from adipocytes in association with lipolysis and may act as an adipokine for the development of insulin resistance and atherosclerosis, leading to cardiovascular events ( 3,9 ). Sitagliptin, a DPP-4 inhibitor, slows GLP-1 degradation, thereby increasing endogenous GLP-1 concentration.…”

“…Finally, we cannot exclude the possibility that the effect of sitagliptin on serum FABP4 level was partly mediated by changes in expression and secretion of FABP4 in cells other than adipocytes. There has been accumulating evidence indicating FABP4 is expressed in several types of cells, in addition to adipocytes and macrophages, under both physiological and pathological conditions ( 3,(51)(52)(53)(54)(55), though the predominant contributors of circulating FABP4 level are adipocytes rather than macrophages or other types of cells ( 3,9 ).…”

Serum Adropin and Adipose Fatty-Acid Binding Protein at 6th Week of Pregnancy Are Significant Predictors for Development of Insulin Resistance at the 24th Week.

“…Despite being intracellular proteins, FABP are released into the circulation and its increased plasma levels had found in several clinical conditions and proposed as markers of tissue injury (6) . Plasma AFABP levels are increased in metabolic disorders as obesity, type-2 diabetes mellitus (9) and cardiovascular conditions (10) , and in critically-ill patients and correlate with poor prognosis (11) .…”