Abstract
IntroductionObesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity.MethodsA total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65) and non-obese (NOB). Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135), corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped.ResultsCompared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values.ConclusionsChildhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.
Highlights
Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children
OB children had higher homeostasis model assessment (HOMA) values, indicative of insulin resistance, and exhibited higher low-density lipoprotein cholesterol (LDL), VLDL, and TG levels and lower high-density lipoprotein (HDL) concentrations compared to NOB children (Table 1)
FABP4 levels were positively correlated with Body mass index (BMI) z score (r:0.57; p < 0.0001). high sensitivity CRP (hsCRP) and HOMA were significantly associated with FABP4 (r = 0.29; p < 0.001 and r = 0.18; p < 0.01, respectively)
Summary
Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. The presence of obesity has been associated with increased levels of high sensitivity CRP (hsCRP) [4], as well as other inflammatory mediators [5,6,7,8,9], all of which promote the development of endothelial and metabolic dysfunction [10,11,12,13,14]. Fatty acid binding proteins (FABP) are a group of related molecules that serve as intracellular chaperones for lipid moieties, coordinate cellular lipid responses, and thereby play a critical role in metabolic and inflammatory pathways [15,16]. Children who are obese are more likely to display elevations in FABP4 plasma levels, which will be reduced by interventions leading to weight loss [21,22]
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