Increased Levels of Adipocyte and Epidermal Fatty Acid-Binding Proteins in Acute Lymphoblastic Leukemia Survivors

Childhood cancer survivors are highly exposed to the development of side effects after many years of cessation of anticancer treatment, including altered lipid metabolism that may result in an increased risk of overweight and metabolic syndrome. Adipocyte (A-FABP) and epidermal (E-FABP) fatty acid-binding proteins are expressed in adipocytes and are assumed to play an important role in the development of lipid disturbances leading to the onset of metabolic syndrome. The aim of this study was to investigate the association between serum A-FABP and E-FABP levels, overweight, and components of the metabolic syndrome in acute lymphoblastic leukemia survivors. Sixty-two acute lymphoblastic leukemia (ALL) survivors (34 females) were included in the study. The mean age at the time of the study was 12.41 ± 4.98 years (range 4.71–23.43). Serum levels of A-FABP and E-FABP were analyzed using a commercially available ELISA kit. The ALL survivors presented statistically higher A-FABP levels in comparison with the healthy controls (25.57 ± 14.46 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with body mass index (BMI) above the normal range (18 overweight, 10 obese) had a greater level of A-FABP compared to the ALL group with normal BMI (32.02 ± 17.10 vs. 20.33 ± 9.24 ng/mL, p = 0.006). Of all participants, 53.23% had at least one risk factor of metabolic syndrome; in this group, only the A-FABP level showed a statistically significant difference compared to the healthy control group (30.63 ± 15.91 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with two or more metabolic risk factors (16.13%) presented higher levels of both A-FABP (33.62 ± 17.16 vs. 15.13 ± 7.61 ng/mL, p = 0.001) and E-FABP (13.37 ± 3.62 vs. 10.12 ± 3.21 ng/mL, p = 0.021) compared to the controls. Univariable regression models showed significant associations between BMI and systolic blood pressure with the A-FABP level (coeff. 1.02 and 13.74, respectively; p < 0.05). In contrast, the E-FABP level was only affected by BMI (coeff. 0.48; p < 0.01). The findings reported herein suggest that the increased levels of A-FABP and E-FABP may be involved in the pathogenesis of overweight and the onset of metabolic syndrome in acute lymphoblastic leukemia. However, further longitudinal, prospective studies of fatty acid-binding proteins and their potential role in the pathogenesis of obesity and metabolic syndrome in ALL survivors remain to be performed.

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Heart and liver fatty acid binding proteins and the metabolic syndrome

Current Hypertension Reports ◽

10.1007/s11906-005-0033-0 ◽

2005 ◽

Vol 7 (6) ◽

pp. 401-406 ◽

Cited By ~ 3

Author(s):

Bert Binas

Keyword(s):

Metabolic Syndrome ◽

Fatty Acid ◽

Binding Proteins ◽

Fatty Acid Binding Proteins ◽

Liver Fatty Acid ◽

Fatty Acid Binding ◽

The Metabolic Syndrome

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Abstract 1319: Plasma Levels of Fatty Acid Binding Proteins 4 and 5 are Markers of Adiposity and the Metabolic Syndrome but are not Independent Predictors of Subclinical Atherosclerosis in Type 2 Diabetes

Circulation ◽

10.1161/circ.116.suppl_16.ii_270-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Roshanak Bagheri ◽

Michael Lehrke ◽

Shiv Kapoor ◽

Megan Wolfe ◽

Karen Terembula ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Fatty Acid ◽

Subclinical Atherosclerosis ◽

Fatty Acid Binding Proteins ◽

Tobit Regression ◽

Fatty Acid Binding ◽

The Metabolic Syndrome ◽

Type 2 Dm

Objectives: Adipocyte-fatty acid binding protein (aP2) or FABP4 is expressed predominantly in adipose and macrophages. Its less abundant family member, FABP5 (Mal1), is more diffusely expressed but also found in adipocytes and macrophages. Gene deletion studies in rodents suggest that FABP4, to a greater extent than FABP5, modulates obesity and atherosclerosis. Preliminary clinical studies support a relationship of circulating FABP4 with obesity and the metabolic syndrome (MetSyn). However, there are no studies of circulating FABPs and atherosclerosis in humans. Methods: We evaluated the association of FABP4 and 5 (ELISA, Biovender) with cardiovascular risk factors, NCEP-defined MetSyn and Coronary Artery Calcification (CAC) in 846 asymptomatic, type 2 DM subjects (62.5% Caucasian, 32.5% African-American; 60% male; aged 58.6±9.2) recruited to the Penn Diabetes Heart Study. Findings : Levels [(median (IQ range)] of FABP4 [37.1 (23.0–55.2) vs 20.9 (14.0–31.0) ng/mL; p<0.001] and FABP5 [1.5 (1.2–1.9) vs 1.4 (1.1–1.8) ng/mL; p<0.01] were higher in women than men. FABP4 was significantly correlated with waist circumference (r=0.4, p<0.001), levels of leptin (r=0.5, p<0.001), insulin (r=0.21, p<0.001), hsCRP (r=0.23, p<0.001), triglycerides (r=0.25, p<0.001) and inversely with HDL cholesterol (women r=−0.23, p<0.001; men r=−0.11, p<0.05). Plasma FABP5 had similar, but weaker biomarker correlations. Both were strongly associated with MetSyn (FABP4 χ 2 =29.8, p<0.0001; FABP5 χ 2 =36.2, p<0.0001). Notably, FABP4 [22.7 (15.0–35.9) vs 34.4 (22.9–55.0), p<0.001], but not FABP5 (p<0.89), levels were lower in subjects on thiazolidinedione therapy. In tobit regression, FABP4, but not FABP5, levels above the median were associated with CAC scores after adjustment for age, gender and ethnicity [1.68 (1.05–2.66), Ratio (CI), p<0.03] but this was attenuated after further adjusting for BMI and established risk factors [1.52 (0.49–2.48), Ratio (CI), p<0.09]. Conclusion: Both FABP 4 and 5 are biomarkers of adiposity and MetSyn. In the first study of its kind, plasma FABP4, but not FABP5, was associated with CAC in type 2 DM, but neither were independent predictors of this subclinical atherosclerosis measure.

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Role of the Fatty Acid Binding Proteins in Cardiovascular Diseases: A Systematic Review

Journal of Clinical Medicine ◽

10.3390/jcm9113390 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3390 ◽

Cited By ~ 1

Author(s):

Hien C. Nguyen ◽

Mohammad Qadura ◽

Krishna K. Singh

Keyword(s):

Fatty Acid ◽

Cardiovascular Diseases ◽

Endothelial Function ◽

Binding Proteins ◽

Blood Lipid ◽

Cell Types ◽

Late Complications ◽

Fatty Acid Binding Proteins ◽

Fatty Acid Binding ◽

The Metabolic Syndrome

Cardiovascular diseases (CVD) remain a global pandemic and leading cause of deaths worldwide. While several guidelines have been developed to control the development of CVDs, its prevalence keeps on increasing until this day. Cardiovascular risk factors, such as reduced exercises and high fat or glucose diets, culminate in the development of the metabolic syndrome and eventually atherosclerosis, which is driven by high blood lipid and cholesterol levels, and by endothelial dysfunction. Late complications of atherosclerosis give rise to serious clinical cardiovascular manifestations such as myocardial infarction and hypertension. Therefore, endothelial functions and the lipid metabolism play critical roles in the pathogenesis of CVDs. Fatty acid-binding proteins are a family of intracellular proteins expressed in many cell types known mainly for their interaction with and trafficking of cellular lipids. The roles of a number of isoforms in this family have been implicated in lipid metabolic homeostasis, but their influence on endothelial function and vascular homeostasis remain largely unknown. This review’s purpose is to update fundamentals about the connection between cardiovascular disease, metabolism, endothelial function, and mainly the roles of fatty acid-binding proteins.

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