Circulating Serum Fatty Acid-Binding Protein 4 Levels Predict the Development of Diabetic Retinopathy in Type 2 Diabetic Patients

Zhang, Xianzhao; Tu, Wen‐Jun; Wang, Hong; Zhao, Qi; Liu, Qiang; Yu, Long-Chuan

doi:10.1016/j.ajo.2017.12.022

Cited by 16 publications

(24 citation statements)

References 43 publications

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“…Lots of potential biomarkers, such as mannose-binding lectin [ 23 ], brain-derived neurotrophic factor [ 24 ], fatty acid binding protein 4 [ 25 ], lipoprotein (a) [ 26 ], and miRNA [ 27–28 ] had been suggested to be associated with DR. Herein, we proposed that RBP4 also was a potential biomarker for DR. Consistent with our findings, another study showed that RBP4 may be involved in the process of DR [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

et al. 2018

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The retinol-binding protein 4 (RBP4) has been postulated to play a role in glucose homeostasis, insulin resistance, and diabetes mellitus in human and animal studies. The aim of the present study was to evaluate the role of RBP4 in Chinese patients with type 2 diabetes mellitus with and without diabetic retinopathy (DR). Plasma RBP4 concentrations were tested in 287 patients with type 2 diabetes. At baseline, demographic and clinical information including presence of DR and vision-threatening DR (VTDR) was collected. The relationship between RBP4 and DR (VTDR) was investigated using logistic regression. Patients with DR or VTDR had significantly higher plasma levels of RBP4 on admission (P<0.0001). Receiver operating characteristics (ROCs) to predict DR and VDTR demonstrated areas under the curve for RBP4 of 0.79 (95% confidence interval (CI): 0.73–0.85) and 0.90 (95% CI: 0.85–0.94), respectively, which were superior to other factors. For each 1 μg/ml increase in plasma level of RBP4, the unadjusted and adjusted risk of DR would be increased by 8% (with the odds ratio (OR) of 1.08 (95% CI: 1.05–1.13), P<0.001) and 5% (1.05 (1.02–1.11), P=0.001), respectively. It was 12% (with the OR of 1.12 (95% CI: 1.07–1.18), P<0.001) and 9% (1.09 (1.05–1.15), P<0.001) for VTDR. The present study shows that elevated plasma levels of RBP4 were associated with DR and VDTR in Chinese patients with type 2 diabetes, suggesting a possible role of RBP4 in the pathogenesis of DR complications. Lowering RBP4 could be a new strategy for treating type 2 diabetes with DR.

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Section: Discussionmentioning

confidence: 99%

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

et al. 2018

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“…FABP4, also referred to in the literature as adipocyte fatty acid-binding protein (AFABP), is a relatively novel adipokine [10], which belongs to the calycin protein superfamily. This protein has also been termed adipocyte P2 (aP2) since there is high sequence similarity (67%) with the myelin P2 protein (M-FABP/FABP8) [11].…”

Section: Fatty Acid-binding Proteinmentioning

confidence: 99%

“…Suppression of PPARγ by FABP4 in visceral fat may explain the reported role of FABP4 in the development of obesity-related morbidities, including insulin resistance, diabetes, and atherosclerosis [35]. The most recent studies also suggest that the FABP4 inhibitor-BMS309403 significantly improves insulin sensitivity in the ob/ob mice, and the FABP4 inhibitor reduces plasma triacylglycerol levels [10].…”

Section: Relationship Between Fabp4 and Pparγmentioning

confidence: 99%

“…It has been reported that increased circulating FABP4 levels are associated with obesity, insulin resistance, T2DM, cardiovascular disorders, arterial hypertension, cardiac dysfunction, kidney damage, fatty liver disease, and atherosclerosis [10,29,31,32,39,40,41,42]. Increased FABP4 concentrations were found in obese subjects and were positively correlated with waist circumference, blood pressure, and insulin resistance [40].…”

Section: Relationship Between Fabp4 and Diseases Of Civilizationmentioning

confidence: 99%

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Associations between Fatty Acid-Binding Protein 4–A Proinflammatory Adipokine and Insulin Resistance, Gestational and Type 2 Diabetes Mellitus

Trojnar

Patro-Małysza

Kimber-Trojnar

et al. 2019

Cells

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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.

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“…Interestingly, females exhibit higher circulating FABP4 levels than males, perhaps suggesting differences in adipose depot contributions and/or the involvement of sex hormones in the regulation of secretion (24). Circulating FABP4 levels have been independently correlated with increased risk for CVDs, early prediction of myocardial infarction (25), poor prognosis following stroke (26), T2D (27), nonalcoholic fatty liver disease (28), worsened glycemic control in type 1 diabetes (29), diabetic complications including retinopathy and nephropathy (30), preeclampsia (31), and association with various cancers, including breast cancer (19) and leukemia (20). Although these associations are robust, the mechanisms underlying how FABP4 contributes to disease pathogenesis remain enigmatic.…”

Section: Hormonal Fabp4mentioning

confidence: 99%

Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses

Prentice

Saksi

Hotamışlıgil

2019

Journal of Lipid Research

117

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Although counterregulatory hormones and mediators of the fight-or-flight responses are well defined at many levels, how energy stores per se are integrated into this system remains an enigmatic question. Recent years have seen the adipose tissue become a central focus for mediating intracellular signaling and communication through the release of a variety of bioactive lipids and substrates, as well as various adipokines. A critical integration node among these mediators and responses is controlled by FA binding protein 4 (FABP4), also known as adipocyte protein 2 (aP2), which is highly expressed in adipose tissue and functions as a lipid chaperone protein. Recently, it was demonstrated that FABP4 is a secreted hormone that has roles in maintaining glucose homeostasis, representing a key juncture facilitating communication between energy-storage systems and distant organs to respond to life-threatening situations. However, chronic engagement of FABP4 under conditions of immunometabolic stress, such as obesity, exacerbates a number of immunometabolic diseases, including diabetes, asthma, cancer, and atherosclerosis. In both preclinical mouse models and humans, levels of circulating FABP4 have been correlated with metabolic disease incidence, and reducing FABP4 levels or activity is associated with improved metabolic health. In this review, we will discuss the intriguing emerging biology of this protein, including potential therapeutic options for targeting circulating FABP4.

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Circulating Serum Fatty Acid-Binding Protein 4 Levels Predict the Development of Diabetic Retinopathy in Type 2 Diabetic Patients

Cited by 16 publications

References 43 publications

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

Associations between Fatty Acid-Binding Protein 4–A Proinflammatory Adipokine and Insulin Resistance, Gestational and Type 2 Diabetes Mellitus

Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses

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