Abstract
There is ample scientific evidence to suggest a link between the fatty acid-binding protein 4 (FABP4) and insulin resistance, gestational (GDM), and type 2 (T2DM) diabetes mellitus. This novel proinflammatory adipokine is engaged in the regulation of lipid metabolism at the cellular level. The molecule takes part in lipid oxidation, the regulation of transcription as well as the synthesis of membranes. An involvement of FABP4 in the pathogenesis of obesity and insulin resistance seems to be mediated via FABP4-dependent peroxisome proliferator-activated receptor γ (PPARγ) inhibition. A considerable number of studies have shown that plasma concentrations of FABP4 is increased in obesity and T2DM, and that circulating FABP4 levels are correlated with certain clinical parameters, such as body mass index, insulin resistance, and dyslipidemia. Since plasma-circulating FABP4 has the potential to modulate the function of several types of cells, it appears to be of extreme interest to try to develop potential therapeutic strategies targeting the pathogenesis of metabolic diseases in this respect. In this manuscript, representing a detailed review of the literature on FABP4 and the abovementioned metabolic disorders, various mechanisms of the interaction of FABP4 with insulin signaling pathways are thoroughly discussed. Clinical aspects of insulin resistance in diabetic patients, including women diagnosed with GDM, are analyzed as well.
Highlights
Type 2 diabetes mellitus (T2DM) represents a common metabolic disorder that is characterized by chronic hyperglycemia
In a study by Thompson et al, the fatty acid-binding protein 4 (FABP4) expression was proven to be significantly increased in animal models of obesity promoted hepatocellular carcinoma (HCC) [97]. These findings are consistent with the previous report, which concluded that peroxisome proliferator-activated receptor γ (PPARγ) is considered a tumor suppressor gene, whereas FABP4 plays a role in tumorigenesis [35]
Abnormalities in the level of FABP4 have been correlated with the development of adiposity, oxidative stress, and atherosclerosis [40]
Summary
Type 2 diabetes mellitus (T2DM) represents a common metabolic disorder that is characterized by chronic hyperglycemia. Insulin resistance is the most powerful predictor of future development of T2DM, but it is a therapeutic target. Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders of pregnancy and its incidence has considerably increased by 10–100% in the last 20 years [1]. It should be emphasized that women with a previous history of GDM have a significantly increased risk of developing T2DM, obesity, and cardiovascular diseases in the future [2,3,4,5]. There is ample evidence to suggest a link between fatty acid-binding protein 4 (FABP4) and insulin resistance, GDM, and T2DM
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