FABP4 in obesity-associated carcinogenesis: Novel insights into mechanisms and therapeutic implications

Abstract

The increasing prevalence of obesity worldwide is associated with an increased risk of various diseases, including multiple metabolic diseases, cardiovascular diseases, and malignant tumors. Fatty acid binding proteins (FABPs) are members of the adipokine family of multifunctional proteins that are related to fatty acid metabolism and are divided into 12 types according to their tissue origin. FABP4 is mainly secreted by adipocytes and macrophages. Under obesity, the synthesis of FABP4 increases, and the FABP4 content is higher not only in tissues but also in the blood, which promotes the occurrence and development of various cancers. Here, we comprehensively investigated obesity epidemiology and the biological mechanisms associated with the functions of FABP4 that may explain this effect. In this review, we explore the molecular mechanisms by which FABP4 promotes carcinoma development and the interaction between fat and cancer cells in obese circumstances here. This review leads us to understand how FABP4 signaling is involved in obesity-associated tumors, which could increase the potential for advancing novel therapeutic strategies and molecular targets for the systematic treatment of malignant tumors.

Single‐cell RNA sequencing reveals aberrant sphingolipid metabolism in non‐small cell lung cancer impacts tumor‐associated macrophages and stimulates angiogenesis via macrophage inhibitory factor signaling

“…Importantly, we found that CXCL10+, CXCR4+, AGER+, and FABP4+ cluster of macrophages may be involved with angiogenesis through cross‐talking with endothelial cells in TME. The fatty acid‐binding protein FABP4, primarily expressed in adipocytes and macrophages, functions as an adipokine 27 . In a recent study, modulation of the intracellular balance of sphingolipid signaling formation in human lung endothelial cells has been reported 28 .…”

“…The fatty acid‐binding protein FABP4, primarily expressed in adipocytes and macrophages, functions as an adipokine. 27 In a recent study, modulation of the intracellular balance of sphingolipid signaling formation in human lung endothelial cells has been reported. 28 The findings presented here provide novel evidence that supports the involvement of TAMs in tumor angiogenesis mediated by SLM.…”

Melanoma cells induce dedifferentiation and metabolic changes in adipocytes present in the tumor niche

“…Mouse melanoma tumors presented a markedly higher growth rate in adiponectin-deficient mice [ 3 ]. Adipocyte protein 2 (FABP4) is expressed in fat cells, where it plays a role as a transporter of fatty acids that facilitates their entry into the plasma membrane, helps in their intracellular transport, and affects lipid and glucose metabolism by increasing fatty acid levels [ 50 ]. Fatty acid synthase (FASN) is engaged in the final steps of the de novo biogenesis of fatty acids and in adipocyte maturation [ 51 , 52 ].…”

A New Insight into Fatty Acid Binding Protein 4 Mechanisms and Therapeutic Implications in Obesity‐Associated Diseases: A Mini Review

“…[26,27] Detection of FABP4 levels higher in obese individuals than in normal-weight individuals; it has been linked with many forms of tumorigenesis, comprising liver, prostate, pancreatic, breast, lung, and ovarian cancers. [21] Excessive FABP4 associated with obesity causes the accumulation of lipids in other organs and can cause lipolysis. [22] In another study, the connotation of FABP4 gene rs1054135 G/A and FABP1 gene rs2241883 A/G polymorphisms with BMI in children and adult populaces was examined and the FABP4 A allele was allied with elevated BMI in children.…”