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Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and
Abdelnaby Khalyfa1, Bharat Bhushan, Mohamed Hegazi
1Department of Pediatrics, Comer Children's Hospital, The University of Chicago, Chicago, IL, USA.
Insights
Childhood obesity is linked to higher levels of FABP4, a protein that may increase cardiometabolic risk. Specific genetic variants in the FABP4 gene might also heighten the risk for insulin resistance and inflammation in obese children.
Area of Science:
- Metabolic Health
- Pediatric Endocrinology
- Genetics
Background:
- Obesity in children is a significant risk factor for developing insulin resistance and metabolic syndrome.
- Fatty acid-binding protein 4 (FABP4) is crucial for glucose and lipid homeostasis, primarily expressed in adipose tissue.
Purpose of the Study:
- To measure plasma FABP4 levels in children with and without obesity.
- To analyze FABP4 gene variants and their association with fasting glucose and insulin.
- To explore the relationship between FABP4, obesity, and metabolic risk factors in children.
Main Methods:
- Recruited 309 children aged 5-7 years, categorized as Obese (OB) or Non-Obese (NOB) based on BMI z-score.
- Measured fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels; calculated HOMA for insulin sensitivity.
- Genotyped four single nucleotide polymorphisms (SNPs) in the FABP4 gene: rs1051231, rs2303519, rs16909233, and rs1054135.
Main Results:
- Obese children exhibited higher FABP4, LDL, hsCRP, and HOMA levels compared to non-obese children.
- FABP4 levels correlated with BMI and contributed to variance in HOMA and hsCRP, but not serum lipids.
- The FABP4 variant rs1051231 was more frequent in obese children and linked to elevated FABP4 levels; variant rs16909233 was associated with increased HOMA.
Conclusions:
- Childhood obesity is associated with elevated FABP4, potentially increasing cardiometabolic risk.
- Specific FABP4 gene SNPs may predispose children to insulin resistance and systemic inflammation in the context of obesity.
Introduction:
Obesity 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.
Methods:
A 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.
Results:
Compared 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.
Conclusions:
Childhood 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.
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