Exploring the mediating role of serum retinol-binding protein 4 in the relationship between sleep quality and insulin resistance in pregnant women.

AIMS: We aimed to explore the mediating role of plasma retinol-binding protein 4 (RBP4) in the relationship between sleep quality and insulin resistance (IR) among pregnant women. METHODS: We conducted a cross-sectional study including 263 pregnant women in the first trimester. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI). The ELISA and homeostasis model assessment (HOMA) was used to analyze plasma RBP4 and estimate IR. The mediating model was used to analyze the mediating role of RBP4 in the relationship between PSQI score and IR. RESULTS: In the multivariable linear regression model, the three terms were positively related with each other, PSQI score was positively associated with IR levels (ß = 0.55, p < 0.05). In the mediating model, RBP4 levels mediated completely the relationship between PSQI scores and IR levels (ß = 0.29, p < 0.0001). The indirect effect of RBP4 in the relation between sleep quality and IR explained 89.10% of total effect. CONCLUSIONS: RPB4 may play a complete mediating role in the relation between sleep quality and insulin resistance in early pregnancy. Improvements in sleep quality in the first trimester may provide a pathway to reduce plasma RBP4, which is beneficial for less IR and GDM prevention.

Retinol-binding protein 4 is closely correlated to blood pressure level and E/A in untreated essential hypertension patients.

BACKGROUND: Hypertension, a common chronic disease, is a leading cause of death and other cardiovascular diseases. Recent studies show that an inflammatory factor named retinol binding protein 4 (RBP4) was increased with cardiovascular diseases. However, the relationship between RBP4 and hypertension in patients remains unclear. METHODS: The study cohort was composed of patients with essential hypertension (EH) and healthy control (HC) subjects from the Second Affiliated Hospital of Nanjing Medical University [2017-2019]. The levels of RBP4 and echocardiography were compared in the current study. Statistical differences between two groups were analyzed using unpaired Student's t-tests and the correlation between the two variables adopts Pearson correlation analysis. SPSS 23.0 was used for all statistical analysis. RESULTS: Analysis of patient plasma samples revealed that RBP4 in EH group was greater than HC group (P<0.05). The area under the ROC curve was 0.717. Specificity and sensitivity were 80.4% and 60.8%, respectively. RBP4 had positive correlation with left ventricular systolic diameter (LVDs), interventricular septal thickness (IVS) and left ventricular posterior wall thickness (LVPW), negative correlation with left ventricular shortening fraction (FS) and ejection fraction (EF) (P<0.05), and no correlation with left ventricular end-diastolic diameter (LVDd) (P>0.05). RBP4 was closely related with E/A, evaluation method of left ventricular diastolic function, in patients with EH. CONCLUSIONS: RBP4 levels are closely correlated with blood pressure (BP) levels and might be involved in the regulation of left ventricular diastolic function in patients with EH.

The role of retinol-binding protein 4 and its relationship with sex hormones in coronary artery disease.

The role of retinol-binding protein 4 (RBP4) in patients with coronary artery disease (CAD) with different sexes has not been clearly established. Sex hormones, especially testosterone (T) and estradiol (E2), have been considered to play an important role in CAD. This study aimed to investigate the role of RBP4 and the possible association between RBP4 and T and E2 in CAD. The study included 658 individuals who underwent coronary angiography (CAG); they were assigned to CAD group (n = 440) and controls (n = 218). CAD group was subdivided into three subgroups. Serum RBP4 and T were assayed by enzyme-linked immunosorbent assay. Serum E2 was measured using electrochemiluminescence immunoassay. For men, RBP4 levels were lower in CAD group, especially those with acute myocardial infarction, than in controls (P < 0.05, P < 0.01, respectively). For women, no significant difference was found in RBP4 levels between both groups. RBP4 was positively correlated with T in male patients with CAD (r = 0.124, P < 0.05). Logistic regression analysis showed that RBP4 was a protective factor for CAD (odds ratio 0.975, 95% confidence interval 0.958-0.993; P = 0.007). In conclusion, RBP4 levels were significantly decreased and positively related with T in men with CAD. Higher RBP4 levels were associated with lower risk of CAD. RBP4 may play a potential protective role for CAD among men.

The Retinol-Binding Protein Receptor 2 (Rbpr2) Is Required for Photoreceptor Survival and Visual Function in the Zebrafish.

Vitamin A/retinol (ROL) and its metabolites (retinoids) play critical roles in eye development and photoreception. Short-term dietary vitamin A deficiency (VAD) manifests clinically as night blindness, while prolonged VAD is known to cause retinal pigment epithelium (RPE) and photoreceptor degeneration. Therefore, sustained uptake of dietary vitamin A, for ocular retinoid production, is essential for photoreceptor health and visual function. The mechanisms influencing the uptake, storage, and supply of dietary vitamin A, for ocular retinoid production, however, are not fully understood. We investigated, in zebrafish, the physiological role of the retinol-binding protein receptor 2 (Rbpr2), for the uptake of dietary ROL, which is necessary for vision. NIH3T3 cells expressing zebrafish Rbpr2 showed plasma membrane localization patterns and were capable of ROL uptake from its bound form. Using whole-mount in situ hybridization, Rbpr2 was found to be expressed exclusively in the liver, intestine, and pancreas, of staged zebrafish larvae. At 5.5 days post fertilization, TALEN-generated rbpr2 mutants (rbpr2 -/- ) had smaller eyes and shorter OS lengths and showed loss of PNA (cones) and rhodopsin (rods) by immunofluorescence staining. Finally, tests for visual function using optokinetic response (OKR) showed no consistent OKR in rbpr2 -/- larval zebrafish. Our analysis, therefore, suggests that Rbpr2 is capable of ROL uptake and loss of this membrane receptor in zebrafish results in photoreceptor defects that adversely affect visual function.

Layer-specific excitation/inhibition balances during neuronal synchronization in the visual cortex.

KEY POINTS: Understanding the balance between synaptic excitation and inhibition in cortical circuits in the brain, and how this contributes to cortical rhythms, is fundamental to explaining information processing in the cortex. This study used cortical layer-specific optogenetic activation in mouse cortex to show that excitatory neurons in any cortical layer can drive powerful gamma rhythms, while inhibition balances excitation. The net impact of this is to keep activity within each layer in check, but simultaneously to promote the propagation of activity to downstream layers. The data show that rhythm-generating circuits exist in all principle layers of the cortex, and provide layer-specific balances of excitation and inhibition that affect the flow of information across the layers. ABSTRACT: Rhythmic activity can synchronize neural ensembles within and across cortical layers. While gamma band rhythmicity has been observed in all layers, the laminar sources and functional impacts of neuronal synchronization in the cortex remain incompletely understood. Here, layer-specific optogenetic stimulation demonstrates that populations of excitatory neurons in any cortical layer of the mouse's primary visual cortex are sufficient to powerfully entrain neuronal oscillations in the gamma band. Within each layer, inhibition balances excitation and keeps activity in check. Across layers, translaminar output overcomes inhibition and drives downstream firing. These data establish that rhythm-generating circuits exist in all principle layers of the cortex, but provide layer-specific balances of excitation and inhibition that may dynamically shape the flow of information through cortical circuits. These data might help explain how excitation/inhibition (E/I) balances across cortical layers shape information processing, and shed light on the diverse nature and functional impacts of cortical gamma rhythms.

Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance.

Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ∼70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle. Hepatokines are proteins that are secreted by hepatocytes, and many hepatokines have been linked to the induction of metabolic dysfunction, including fetuin A, fetuin B, retinol-binding protein 4 (RBP4) and selenoprotein P. In this Review, we describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication.

Increased retinol-free RBP4 contributes to insulin resistance in gestational diabetes mellitus.

PURPOSE: Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. METHODS: Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats. After then, normal pregnant rats were divided into two groups to receive either apo-RBP4 or vehicle injection. The metabolic parameters and insulin signaling in adipose tissue, skeletal muscle and liver were determined in apo-RBP4 and control groups. Primary human adipocytes were cultured in vitro with different proportions of apo-RBP4 and holo-RBP4 for 24 h. The interaction between RBP4 and STRA6 was assessed by co-immunoprecipitation, and the expression of JAK-STAT pathway and insulin signaling were detected by Western blotting and immunofluorescence. RESULTS: We found increases in serum RBP4 levels and the RBP4:retinol ratio but not in the retinol levels in GDM rats. Exogenous apo-RBP4 injection attenuated insulin sensitivity in pregnant rats. In vitro, a prolonged interaction between RBP4 and STRA6 was observed when apo-RBP4 was present. In response to increased apo-RBP4 levels, cells showed elevated activation of the JAK2/STAT5 cascade and SOCS3 expression, decreased phosphorylation of IR and IRS1, and attenuated GLUT4 translocation and glucose uptake upon insulin stimulation. CONCLUSION: Apo-RBP4 is a ligand that activates the STRA6 signaling cascade, inducing insulin resistance in GDM.

RBP4 functions as a hepatokine in the regulation of glucose metabolism by the circadian clock in mice.

AIMS/HYPOTHESIS: As one of the key adipokines, retinol binding protein 4 (RBP4) is suggested to positively correlate with insulin resistance; however, not all clinical studies support this association. Although some explanations are proposed for this discrepancy, the temporal aspect of RBP4 secretion has not been considered. Aryl hydrocarbon receptor nuclear translocator-like (also known as BMAL1) and its target D site-binding protein (DBP) are both pivotal transcription factors of the circadian core clock. Given the overwhelming presence of circadian control in metabolism and the principal role of the liver in RBP4 secretion, we hypothesised that RBP4 may oscillate under the control of BMAL1 and act as a hepatokine, participating in the maintenance of glucose homeostasis by the circadian clock. METHODS: We used liver-specific Bmal1 (also known as Arntl)-knockout mice and recombinant adenoviruses expressing short-hairpin RNA (shRNA) specific for Dbp or Rbp4 in the liver. RESULTS: RBP4 displayed diurnal oscillations in the liver and plasma, which were dampened in liver-specific-Bmal1-knockout mice. BMAL1 regulated hepatic RBP4 expression via its direct target, DBP. Hepatic knockdown of RBP4 or DBP increased whole-body insulin sensitivity in mice in a time-of-day-dependent manner. Conversely, hepatic overexpression of RBP4 reversed the insulin-sensitising effects of liver-specific depletion of BMAL1. CONCLUSIONS/INTERPRETATION: Our results not only provide a novel mechanism for circadian regulation of RBP4, but also unveil a critical role of RBP4, acting as a hepatokine in the regulation of glucose metabolism by the circadian clock.

Retinol binding protein 4 in relation to diet, inflammation, immunity, and cardiovascular diseases.

Retinol binding protein 4 (RBP4), previously called retinol binding protein (RBP), is considered a specific carrier of retinol in the blood. It is also an adipokine that has been implicated in the pathophysiology of insulin resistance. RBP4 seems to be correlated with cardiometabolic markers in inflammatory chronic diseases, including obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases (CVDs). It has recently been suggested that inflammation produced by RBP4 induces insulin resistance and CVD. The clinical relevance of this hypothesis is discussed in this review. Knowledge concerning the association of RBP4 with inflammation markers, oxidative stress, and CVDs as well as concerning the role of diet and antioxidants in decreasing RBP4 concentrations are discussed. Special attention is given to methodologies used in previously published studies and covariates that should be controlled when planning new studies on this adipokine.

Adipokines as drug targets in diabetes and underlying disturbances.

Diabetes and obesity are worldwide health problems. White fat dynamically participates in hormonal and inflammatory regulation. White adipose tissue is recognized as a multifactorial organ that secretes several adipose-derived factors that have been collectively termed "adipokines." Adipokines are pleiotropic molecules that gather factors such as leptin, adiponectin, visfatin, apelin, vaspin, hepcidin, RBP4, and inflammatory cytokines, including TNF and IL-1ß, among others. Multiple roles in metabolic and inflammatory responses have been assigned to these molecules. Several adipokines contribute to the self-styled "low-grade inflammatory state" of obese and insulin-resistant subjects, inducing the accumulation of metabolic anomalies within these individuals, including autoimmune and inflammatory diseases. Thus, adipokines are an interesting drug target to treat autoimmune diseases, obesity, insulin resistance, and adipose tissue inflammation. The aim of this review is to present an overview of the roles of adipokines in different immune and nonimmune cells, which will contribute to diabetes as well as to adipose tissue inflammation and insulin resistance development. We describe how adipokines regulate inflammation in these diseases and their therapeutic implications. We also survey current attempts to exploit adipokines for clinical applications, which hold potential as novel approaches to drug development in several immune-mediated diseases.

Associations between tissue visfatin/nicotinamide, phosphoribosyltransferase (Nampt), retinol binding protein-4, and vaspin concentrations and insulin resistance in morbidly obese subjects.

Visfatin/Nampt, vaspin, and retinol binding protein-4 (RBP-4) play an important role in insulin resistance. The objectives of this study were to measure visfatin/Nampt, vaspin, and RBP-4 concentrations in blood, liver, muscle, subcutaneous, omental, and mesenteric adipose tissues in morbidly obese subjects and investigate their relationship to insulin resistance. Blood and tissue samples were collected from 38 morbidly obese subjects during Roux-en-Y surgery. Insulin resistance biomarkers were measured using standard kits. Visfatin/Nampt, vaspin, and RBP-4 gene expression levels in tissues were measured using real-time PCR. Their protein concentrations in blood and tissues were measured using ELISA kits. Diabetic subjects had significantly higher homeostasis model of assessment-insulin resistance and age and lower blood HDL-cholesterol concentrations than nondiabetic and prediabetic subjects. Diabetic and prediabetic subjects had significantly higher blood concentrations of visfatin/Nampt and vaspin than nondiabetic subjects. Liver RBP-4 concentrations were positively associated with blood glucose concentrations. Blood insulin resistance biomarker levels were positively associated with visfatin/Nampt concentrations in omental adipose tissue and liver, and vaspin concentrations in mesenteric adipose tissue. In conclusion, the correlations of visfatin/Nampt, vaspin, and RBP-4 with insulin resistance are tissue dependent.

High fat diet induced insulin resistance and elevated retinol binding protein 4 in female rats; treatment and protection with Berberis vulgaris extract and vitamin A.

This research was conducted to investigate two main aims; the first aim was to find if there is a relationship between insulin resistance (IR) and retinol binding protein 4 (RBP4). The second aim was to use berberis vulgaris extract and vitamin A as protective and/or curative agents against insulin resistance. IR was developed by feeding the female rats a high fat diet (HFD) for six weeks then treating or protecting them with b. vulgaris extract (0.2 g/Kg body weight) or vitamin A (12.8µg/Kg/day) for two weeks. HFD intake elevated insulin level and RBP4 expression that associated with hyperglycemia and hyperlipidemia. Co-administration of vitamin A and B. vulgaris extracts reduced blood glucose level, insulin, body weight and RBP4 expression before, during and after HFD. Furthermore, vitamin A reduced the blood glucose, triglycerides (TG) and cholesterol levels. IR syndrome associated with the RBP 4 alteration that gives high indication about the role of RBP4 expression in the IR progression and development. Furthermore, the treatment with vitamin A and/or b. vulgaris alleviated the IR syndrome through the action on RBP4 and Insulin secretion. On the other hand, vitamin A must be avoided for the predisposed IR and prediabetic patients.

The association of retinol-binding protein 4 with metabolic syndrome and obesity in adolescents: the effects of gender and sex hormones.

OBJECTIVES: Retinol-binding protein 4 (RBP4) has a role in the development of insulin resistance (IR), type 2 diabetes, obesity, and metabolic syndrome among adults. However, data among adolescents are limited, and the effects of gender and sex hormones on RBP4 are not well defined. MATERIALS/METHODS: A total of 1082 adolescents were enrolled and categorized based on their body mass index. Blood samples were collected, and biochemical characteristics, sex hormones, RBP4 concentrations, and IR were determined. RESULTS: Testosterone and estradiol were not directly correlated with RBP4 concentrations in both genders. Multivariate regression analysis revealed that fasting plasma glucose (FPG), triglyceride (TG), and testosterone levels were independently associated with RBP4 concentrations in boys; also, there was a trend of increasing RBP4 levels with the severity of obesity. CONCLUSION: Plasma RBP4 concentrations correlated with obesity and cardiovascular risk factors, predominantly evident in boys. Testosterone, FPG, and TG levels were independent predictors of RBP4 concentrations.

Association of serum retinol-binding protein 4 with insulin resistance and metabolic parameters during olanzapine therapy.

OBJECTIVE: Retinol-binding protein 4 (RBP4) has been shown to be associated with insulin resistance (IR), metabolic indices and metabolic syndrome (MetS) in various patient populations and in obesity. We investigated the association between metabolic parameters, IR and RBP4 during olanzapine therapy. DESIGN: A prospective study. PATIENTS: Thirty-seven participants with psychiatric disorder who were atypical antipsychotic naive and newly initiated on olanzapine were assessed. MEASUREMENTS: Fasting RBP4, anthropometric and metabolic variables were measured before and after 3 months of olanzapine therapy. RESULTS: Participants who developed MetS showed higher RBP4 levels compared with those without MetS, although not significant (P = 0·053). The variation in RBP4 level was correlated with changes in systolic blood pressure (r = 0·423, P = 0·009), diastolic blood pressure (r = 0·390, P = 0·017), total cholesterol (r = 0·446, P = 0·006) and low-density lipoprotein (LDL) (r = 0·407, P = 0·012). Multiple linear regression analysis illustrated that end-point log insulin level was the most significant independent predictor of final log RBP4 levels (standardized ß = 0·353, P = 0·024). CONCLUSIONS: Our results suggest that RBP4 levels might be associated with at least some olanzapine-induced metabolic abnormalities and cardiovascular disease risk factors.

RBP4: a controversial adipokine.

Adipose tissue is an endocrine organ secreting biologically active factors called adipokines that act on both local and distant tissues. Adipokines have an important role in the development of obesity-related comorbidities not only in adults but also in children and adolescents. Retinol binding protein 4 (RBP4) is a recently identified adipokine suggested to link obesity with its comorbidities, especially insulin resistance, type 2 diabetes (T2D), and certain components of the metabolic syndrome. However, data, especially resulting from the clinical studies, are conflicting. In this review, we summarize up-to-date knowledge on RBP4's role in obesity, development of insulin resistance, and T2D. Special attention is given to studies on children and adolescents. We also discuss the role of possible confounding factors that should be taken into account when critically evaluating published studies or planning new studies on this exciting adipokine.

Retinol-binding protein 4 : a possible role in cardiovascular complications.

BACKGROUND AND PURPOSE: Retinol-binding protein 4 (RBP4) is an adipocyte-secreted hormone proposed to link obesity with insulin resistance. However, the role of RBP4 in cardiovascular complications is yet to be fully understood. The present study is aimed to decipher the association between RBP4 with pro-inflammatory cytokines and low-density lipoprotein (LDL) cholesterol in diet-induced obese and hyperlipidaemic mice. To understand the correlation, rimonabant, an anti-obesity drug, has been used to relieve the atherosclerotic predisposition. EXPERIMENTAL APPROACH: Adipose and/or aortic tissue expressions of RBP4, pro-inflammatory cytokine genes and circulating LDL levels were measured in high fat (HF)-fed female C57BL/6 and high cholesterol (HC)-fed apolipoprotein E3 (ApoE3) Leiden mice. KEY RESULTS: Mice fed a HF diet had a significantly increased adipose expression of RBP4, TNF-α and monocyte chemoattractant protein 1 (MCP-1) and down-regulated adiponectin mRNA levels. A significant increase in aortic RBP4 and MCP-1 expression and circulating levels of LDL and C-reactive protein (CRP) was found in the ApoE3 mice fed a HC diet. Interestingly, rimonabant treatment lowered the elevated aortic RBP4, MCP-1 expressions and significantly reduced the serum levels of LDL, CRP, RBP4 and MCP-1. CONCLUSION AND IMPLICATIONS: Our results indicate that RBP4 is positively associated with markers of inflammation in obese and pro-atherogenic conditions and could play a role in a predisposition to atherosclerosis. Furthermore, our results indicate that rimonabant may improve vascular function by modulating RBP4 along with pro-inflammatory cytokines.

Effects of retinol binding protein-4 on vascular endothelial cells.

The study was designed to investigate the effect of retinol binding protein (RBP)-4 on the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways, which mediate the effects of insulin in vascular endothelial cells. The effects of RBP4 on nitric oxide (NO) and insulin-stimulated endothelin-1 (ET-1) secretion and on phosphorylation (p) of Akt, endothelial NO synthetase (eNOS), and extracellular signal-regulated kinase (ERK)1/2 were investigated in bovine vascular aortic endothelial cells (BAECs). RBP4 showed an acute vasodilatatory effect on aortic rings of rats within a few minutes. In BAECs, RBP4-treatment for 5min significantly increased NO production, but inhibited insulin-stimulated ET-1 secretion. RBP4-induced NO production was not inhibited by tetraacetoxymethylester (BAPTA-AM), an intracellular calcium chelator, but was completely abolished by wortmannin, a PI3K inhibitor. RBP4 significantly increased p-Akt and p-eNOS production, and significantly inhibited p-ERK1/2 production. Triciribine, an Akt inhibitor, and wortmannin significantly inhibited RBP4-induced p-Akt and p-eNOS production. Inhibition of Akt1 by small interfering RNA decreased p-eNOS production enhanced by RBP4 in human umbilical vein endothelial cells. In conclusion, RBP4 has a robust acute effect of enhancement of NO production via stimulation of part of the PI3K/Akt/eNOS pathway and inhibition of ERK1/2 phosphorylation and insulin-induced ET-1 secretion, probably in the MAPK pathway, which results in vasodilatation.

Serum adipocyte fatty acid-binding protein, retinol-binding protein 4, and adiponectin concentrations in relation to the development of the metabolic syndrome in Korean boys: a 3-y prospective cohort study.

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP), retinol-binding protein 4 (RBP4), and adiponectin have been associated with insulin resistance and the metabolic syndrome in adults. OBJECTIVE: We evaluated the association of A-FABP, RBP4, and adiponectin with the metabolic syndrome in Korean boys. DESIGN: In this prospective cohort study, 159 boys participated in a school-based health examination and were followed up after 3 y. The metabolic syndrome in children was defined by using the pediatric adaptation of the National Cholesterol Education Program criteria. RESULTS: Compared with normal-weight participants, overweight children had significantly higher A-FABP (23.6 ± 8.2 compared with 12.8 ± 5.1 µg/L, P < 0.001) and RBP4 (69.3 ± 17.1 compared with 59.7 ± 15.3 µg/mL, P = 0.001) concentrations and significantly lower adiponectin concentrations (11.5 ± 5.4 compared with 18.1 ± 8.4 µg/mL, P < 0.001). Baseline A-FABP concentrations were significantly higher in children who developed the metabolic syndrome than in those who did not, whereas adiponectin concentrations were significantly lower. Baseline RBP4 concentrations were not significantly different between the 2 groups. Multiple logistic regression analysis showed that only A-FABP was an independent predictor of the development of the metabolic syndrome after adjustment for Tanner stage, insulin resistance, body mass index, sleep duration, and physical activity (odds ratio: 17.3; 95% CI: 1.25, 239.76; highest compared with lowest tertile), whereas the significant association between adiponectin and the metabolic syndrome observed by using bivariate analysis reflects, in part, an underlying association with obesity. CONCLUSION: A-FABP predicts the development of the metabolic syndrome independently of pubertal status, adiposity, and insulin resistance in Korean boys.