C-reactive protein expression in adipose tissue of children with acute appendicitis.

OBJECTIVE: The aim of this study is to gain insights into the role of visceral adipose tissue as a source of C-reactive protein (CRP) in acute inflammation and to explore the potential relationship of CRP expression with the severity of appendicitis. METHODS: A total of 20 pediatric patients undergoing appendectomy were included in the study. Patients were divided into two groups according to appendicitis severity (uncomplicated and complicated). CRP levels were measured in visceral fat samples by western blotting, as well as in serum by biochemical testing. RESULTS: CRP was found to be expressed in visceral adipose tissue. The adipose tissue of patients with complicated appendicitis showed significantly higher CRP levels (p = 0.002) compared to patients with uncomplicated appendicitis. These results mirrored the CRP values obtained in serum (p = 0.018). CONCLUSION: In childhood, visceral adipose tissue is a source of CRP in acute inflammation, and its expression is potentially associated with the severity of local inflammation.

Relationship between polymorphisms in the CRP, LEP and LEPR genes and high sensitivity C-reactive protein levels in Spanish children.

BACKGROUND: We investigated the association of single nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP), leptin (LEP) and leptin receptor (LEPR) genes with high sensitivity CRP (hs-CRP) levels in two independent cohorts of healthy Spanish children. METHODS: We measured hs-CRP levels in 646 6-8-year-old and 707 12-16-year-old children using a high-sensitivity C-Reactive Protein ELISA kit. Four SNPs in the CRP gene (rs1205, rs1130864, rs2794521 and rs1800947), one SNP in the LEP gene (rs7799039) and two SNPs in the LEPR (rs1137100 and rs1137101) gene were determined by TaqMan® allelic discrimination assays. RESULTS: The four CRP SNPs studied were significantly (p<0.05) associated with hs-CRP levels in both cohorts. Furthermore, two common CRP haplotypes (constructed using the SNPs in order: rs1205, rs1130864, rs1800947, rs2794521) ACGA and GCGG were associated with significantly lower CRP levels (p<0.05) at both ages. The LEPR SNPs rs1137100 (K109R) and rs1137101 (Q223R), and LEP SNP rs7799039 (G2548A) were also associated to hs-CRP levels (p<0.05) in both cohorts. CONCLUSIONS: hs-CRP levels in healthy Spanish children, besides being associated to common polymorphisms in the CRP gene, are associated to polymorphisms in the LEP and LEPR genes, which suggests that other loci, in addition the CRP gene, may have a role determining CRP levels in children.

High-Sensitivity C-Reactive Protein and Leptin Levels Related to Body Mass Index Changes Throughout Childhood.

OBJECTIVES: To analyze the association between high-sensitivity C-reactive protein (hs-CRP) levels and cardiovascular risk factors in healthy school children, and to evaluate whether changes in body mass index (BMI) category throughout childhood affect hs-CRP levels. STUDY DESIGN: We measured serum hs-CRP levels, lipid profile, insulin levels, and leptin levels in 683 prepubertal children and 748 adolescents. A total of 272 children participated in the study in both cohorts, prepubertal (baseline; age 6-8 years) and adolescents (follow-up; age 12-16 years). RESULTS: Compared with their normal weight (NW) counterparts, hs-CRP levels were significantly higher in obese and overweight (OW) adolescents and obese prepubertal children. The highest hs-CRP levels were seen in children who were OW at baseline and at follow-up, and the lowest levels in those who transitioned from OW at baseline to NW at follow-up. High-density lipoprotein cholesterol and apolipoprotein A-I levels decreased across the hs-CRP tertile in both prepubertal children and adolescents, with significant differences (P < .001) in concentrations between the highest and lowest tertiles in 6- to 8-year-old boys and girls and in 12- to 16-year-old boys. The hs-CRP levels were also significantly associated with leptin levels in both prepubertal children and adolescents, with a significant increase across hs-CRP tertiles (P < .001). CONCLUSIONS: The shift from OW to NW throughout childhood is associated with a decrease in hs-CRP level to below that observed in children who maintain NW throughout childhood. Leptin levels were strongly associated with hs-CRP levels in our population independent of BMI. Our findings suggest that an obesity-related chronic inflammatory state may be reversible by improving weight status.

Sex-related differences in the association of ghrelin levels with obesity in adolescents.

BACKGROUND: The utility of ghrelin as a biomarker may be different depending on gender. The aim of this study was to assess ghrelin levels in a population-based sample of adolescents, and to evaluate their association with obesity and obesity-related parameters depending on sex. METHODS: The studied population included 601 randomly selected 14-to 16-year-old children. Anthropometrical data were measured and body mass index (BMI) and waist to hip ratio calculated. Body composition was assessed using an impedance body composition analyzer. Total serum ghrelin levels were determined using a multiplexed bead immunoassay. Serum leptin and adiponectin levels were determined by ELISA and insulin by RIA. RESULTS: Ghrelin levels were significantly higher in girls than in boys. Serum ghrelin concentrations were significantly lower (p<0.01) in obese than in normal weight (NW) girls, but showed no differences by weight category in boys. Ghrelin showed a significant negative relationship with waist circumference (WC), waist to hip ratio and fat mass (p<0.05) in both genders, and with weight and BMI (p<0.01) in girls, and insulin (p<0.01) and HOMA (p<0.05) in boys. Ghrelin also correlated negatively with leptin levels in girls (p<0.01). CONCLUSIONS: Our study describes serum ghrelin levels in adolescents, showing a sexual dimorphism in ghrelin levels in these 14-to 16-year-old children, and a different association of ghrelin levels with obesity by gender that suggests a different appetite and energy expenditure control depending on sex at this age.

Association of resistin polymorphisms with resistin levels and lipid profile in children.

Previous research has found a correlation between resistin and lipid level variations. Polymorphisms in the resistin gene (RETN) could be involved in this relationship, but the results of the different studies are contradictory. The aim of this study was to examine the association between resistin and lipid levels, and to determine whether resistin polymorphisms are associated with resistin levels and lipid profile in prepubertal children and adolescents. The single nucleotide polymorphisms (SNPs) rs1862513 and rs10401670 were analyzed in 442 randomly selected 6- to 8-year-old children and 827 children aged 12-16 years. Anthropometric data were recorded. Lipid profile was determined using standard methods. Serum resistin levels were measured using a multiplexed bead immunoassay. Resistin polymorphisms were determined by TaqMan(®) allelic discrimination assays. A relationship was found between serum levels of resistin and the SNP rs10401670 in 6- to 8-year-old boys. SNP rs10401670 was also related to TC and LDL-cholesterol in 12- to 16-year-old boys and to HDL-C in 12- to 16-year-old girls. SNP rs1862513 was not related to any of the studied variables. Serum resistin levels were significantly and negatively associated with ApoAI levels in 12- to 16-year-old girls. A SNP in the 3'UTR region of RETN (rs10401670) is associated with resistin levels and lipid profile in children, showing different associations depending on age and gender.

Sleep problems and circadian rhythm functioning in autistic children, autism with co-occurring attention deficit hyperactivity disorder, and typically developing children: A comparative study.

LAY ABSTRACT: Sleep problems are common in autism spectrum disorder (ASD) and different factors can contribute to its occurrence in this population. Misalignment of the biological clock (our circadian system) has been described as one possible explanation. While there is a body of research on sleep problems, relatively less is known about circadian functioning and the specific population of autistic children with co-occurring attention deficit hyperactivity disorder (ADHD). Using an ambulatory circadian monitoring (ACM) system, which resembles a common watch, we gathered sleep parameters and the different rhythms obtained from measuring motor activity, light exposure and distal temperature in 87 autistic children and adolescents, 27 of whom were diagnosed with co-occurring ADHD, and 30 neurotypical children and adolescents as a comparison group. Autistic children and, especially, those with co-occurring ADHD showed greater motor activity during sleep which would be worth studying in future projects which could better define this restless sleep. Of note, we observed an atypical pattern of wrist temperature, with higher values in neurotypical children, followed by autistic children and, ultimately, those with co-occurring ADHD. Temperature is one of the most valuable factors evaluated here as it is closely connected to sleep-wakefulness and the hormone melatonin. Its special pattern during day and nighttime would support the hypothesis of an atypical secretion of melatonin in autistic individuals which would also link with the higher presence of sleep problems in this neurodevelopmental condition.

Sleep Problems, Circadian Rhythms, and Their Relation to Behavioral Difficulties in Children and Adolescents with Autism Spectrum Disorder.

This was an exploratory cross-sectional study comparing 45 children with ASD to 24 typically developing drug-naïve controls, group-matched on age, sex, and body mass index. Objective data was obtained using the following: an ambulatory circadian monitoring device; saliva samples to determine dim light melatonin onset (DLMO): and three parent-completed measures: the Child Behavior Checklist (CBCL); the Repetitive Behavior Scale-Revised (RBS-R); and the General Health Questionnaire (GHQ28). The CBCL and RBS-R scales showed the highest scores amongst poor sleepers with ASD. Sleep fragmentation was associated with somatic complaints and self-injury, leading to a higher impact on family life. Sleep onset difficulties were associated with withdrawal, anxiety, and depression. Those with phase advanced DLMO had lower scores for "somatic complaints"; "anxious/depressed" state; and "social problems", suggesting that this phenomenon has a protective role.

Leptin Concentrations Determine the Association between High-Sensitivity C-Reactive Protein Levels and Body Mass Index in Prepubertal Children.

Obesity is associated with the presence of low-grade inflammation even during childhood. The dysregulation in the secretion of adipokines, such as leptin, which occurs in obesity states, could be associated with an increase in inflammatory factors already at an early age. In this cross-sectional study, we aimed to investigate the role of leptin levels in the association between body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) in healthy schoolchildren. Leptin and hs-CRP levels were analyzed in two pediatric cohorts comprising 684 prepubertal children and 763 adolescents. hs-CRP concentrations correlated significantly with BMI and leptin levels in prepubertal males and females as well as in adolescents. However, after adjusting for leptin concentration, no significant correlation was observed between hs-CRP and BMI in prepubertal children, while the correlations remained significant in adolescents. The same differences were observed when analyzed BMI according to hs-CRP tertile after adjusting for leptin; mean BMI was not significantly different between hs-CRP tertile in prepubertal children but was significantly different in adolescents. In conclusion, the fact that leptin concentrations determine the association of BMI with hs-CRP levels in prepubertal children, but not in adolescents, suggests a role for leptin in low-grade inflammation at early ages, while other factors seem to contribute to hs-CRP levels later in life.

Response to Melatonin Treatment in Children With Autism spectrum Disorder and Relationship to Sleep Parameters and Melatonin Levels.

Melatonin is one of the most used pharmacologic treatments for sleep problems in autism spectrum disorder, though its relationship with circadian and sleep parameters is still not well stablished. A naturalistic study was conducted in children with autism spectrum disorder, previously drug-naïve, before and after treatment with immediate-release melatonin. Circadian rhythms and sleep parameters were studied using an ambulatory circadian-monitoring device, and saliva samples were collected enabling determination of dim light melatonin onset. Twenty-six children with autism spectrum disorder (age 10.50 ± 2.91) were included. Immediate-release melatonin modified circadian rhythm as indicated by wrist skin temperature, showing an increase at night. A positive correlation was found between time of peak melatonin and sleep efficiency improvement values. Sleep-onset latency and efficiency improved with immediate-release melatonin. Immediate-release melatonin could be an effective treatment to improve sleep onset and restore a typical pattern of wrist temperature, which appears to be lost in autism spectrum disorder.

Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children.

Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been linked to energy and lipid homeostasis. The aim of our study was to evaluate the associations of CLOCK and REV-ERBα SNPs with BMI and plasma lipid levels in pre-pubertal boys and girls. The study sample population comprised 1268 children aged 6-8 years. Information regarding anthropometric parameters and plasma lipid concentrations was available. Genotyping of CLOCK SNPs rs1801260, rs4580704, rs3749474, rs3736544 and rs4864548 and REV-ERBα SNPs rs2017427, rs20711570 and rs2314339 was performed by RT-PCR. The CLOCK SNPs rs3749474 and rs4864548 were significantly associated with BMI in girls but no in boys. Female carriers of the minor alleles for these SNPs presented lower BMI compared to non-carriers. A significant association of the REV-ERBα SNP rs2071570 with plasma total cholesterol, LDL-cholesterol and Apo B in males was also observed. Male AA carriers showed lower plasma levels of total cholesterol, LDL-cholesterol and Apo B levels as compared with carriers of the C allele. No significant associations between any of the studied REV-ERBα SNPs and plasma lipid levels were observed in females. In summary, CLOCK and REV-ERBα SNPs were associated with BMI and plasma lipid levels respectively in a sex-dependent manner. Our findings suggest that sex-related factors may interact with Clock genes SNPs conditioning the effects of these polymorphisms on circadian alterations.

Relationship between eating habits, sleep patterns and physical activity and the degree of obesity in children and adolescents.

INTRODUCTION: Childhood obesity is an extremely prevalent pathology and, in order to be able to address it, it is necessary to understand the factors that influence on its genesis and maintenance. We hypothesise that the timing of meals and sleep, the regularity of these throughout the week and a sedentary lifestyle influence the degree of obesity. MATERIAL AND METHODS: We included children and adolescents with obesity who attended a first check-up visit at the Childhood Obesity Unit between January 2018 and February 2020. The data were obtained from a questionnaire on food (36-h intake, frequency of consumption, eating times and habits) and sleep. RESULTS: The degree of obesity was influenced to a greater extent by later meal times and the distribution of calories throughout the day (less at breakfast, more at dinner) than by the total number of calories ingested. In addition, a lower consumption of vegetables was related to a higher degree of obesity. The difference between the hours of sleep at weekends and on weekdays correlated positively with a higher degree of obesity. Finally, the anthropometric data correlated negatively with the number of hours of physical activity. Almost half of the children did not exercise after school. CONCLUSION: In the approach to childhood obesity, it is necessary to include recommendations on the regularity of meal and sleep times, as well as the distribution of calories throughout the day. Additionally, it is necessary to encourage the practice of physical exercise.

Prevalence and risk factors associated with different comorbidities in obese children and adolescents.

INTRODUCTION: Different obesity-related comorbidities already present in childhood, such as: vitamin D deficiency, impaired carbohydrate metabolism, dyslipidaemia, arterial hypertension and non-alcoholic steatohepatitis. In this study, we aim to analyse the prevalence of comorbidities and to determine the predictive factors that affect these comorbidities. MATERIAL AND METHODS: Anthropometric, demographic and biochemical variables were collected from obese patients between six and 18 years of age. Subsequently, a statistical analysis was performed to describe the characteristics of the patients and the prevalence of comorbidities, as well as their predictive factors. RESULTS: A total of 158 obese children (76 boys and 82 girls) with a mean age at diagnosis of 12.48 years and a BMI Z-score of +3.24 SDS were included. The most prevalent comorbidities were vitamin D deficiency (64.2%), insulin resistance (45.1%), dyslipidaemia (32.2%), hyperuricaemia (18.5%) and arterial hypertension (15%). Age, BMI Z-score, percentage of fat mass and male sex have been found to be predictors of these comorbidities. CONCLUSION: Obese children and adolescents have a high prevalence of comorbidities. Once the diagnosis of obesity has been established, it would be very useful to identify early those patients with a higher risk of comorbidities, knowing their relationship with sex, age, BMI Z-score, percentage of fat mass and pubertal stage.

Sleep Problems and Circadian Functioning in Children and Adolescents With Autism Spectrum Disorder.

BACKGROUND: Sleep problems are a prevalent comorbidity in autism spectrum disorder (ASD) with a multifactorial basis in which circadian misalignment has been described. METHODS: A cross-sectional study was conducted including 52 children and adolescents with ASD (9.85 ± 3.07) and 27 children and adolescent controls with normal intellectual functioning (8.81 ± 2.14). They were matched for age, sex, and body mass index, and all were drug-naïve. An ambulatory circadian monitoring device was used to record temperature and motor, body position, sleep, and light intensity. RESULTS: Individuals with ASD presented longer sleep-onset latency, lower sleep efficiency, and decreased total sleep time and tended to be more sedentary and have less exposure to light. They also showed lower amplitude, low interdaily stability, and a different pattern of wrist temperature across the day, with a midpoint of sleep that did not concur with sleep midpoint indicated by the rest of circadian parameters. CONCLUSIONS: The sleep problems observed in this sample resemble those reported previously, with the exception of nocturnal awakenings which did not show differences. The ambulatory circadian monitoring device enabled measurement of circadian parameters such as temperature which, until now, were scarcely described in children with ASD and could be used to better understand sleep and circadian system in ASD.

Adult Height in Girls With Idiopathic Premature Adrenarche: A Cohort Study and Design of a Predictive Model.

Introduction: Idiopathic premature adrenarche (IPA) is considered a normal variant of puberty, presenting more commonly in female patients. There are concerns as to whether IPA alters the final height of these girls. Our main objectives were to (a) compare the adult height of girls with IPA against their target height and (b) design a mathematical model to predict adult height at diagnosis in female patients with IPA. Materials and Methods: A cohort study of girls with IPA was conducted from the time of IPA diagnosis until adult height. The following data were collected: target height, perinatal history, anthropometric and biochemical variables and bone age at diagnosis, age at Tanner stage 2 and menarcheal age, and adult height. First, we performed a univariate statistical analysis after which we carried out a multiple linear regression analysis using adult height as the dependent variable. Results: We obtained data from 79 female patients diagnosed with IPA with a mean adult height of 164.6 cm (95% CI: 163.36-165.85 cm). The mean follow-up time was 6.60 years. Average age at Tanner stage 2 was 9.71 years. Mean menarcheal age was 11.64 years. There were no significant differences between target height and adult height. Of the several predictive models designed for these patients, one of them, which included bone age, obtained an R2 value of 71%. Conclusions: Although slightly advanced puberty was observed among the girls with IPA, their adult height was preserved. The use of predictive models of adult height on diagnosis of IPA could facilitate closer follow-up of girls at risk of reduced adult height.

Melatonin Rhythm and Its Relation to Sleep and Circadian Parameters in Children and Adolescents With Autism Spectrum Disorder.

Introduction: Sleep problems are prevalent among individuals with autism spectrum disorder (ASD), and a role has been attributed to melatonin in this multifactorial comorbidity. Methods: A cross-sectional study was conducted on 41 autistic children and adolescents (9.9 ± 3.02) and 24 children and adolescents with a normal intellectual function (8.42 ± 2.43) were used as controls. Subjects were matched for sex, body mass index, and pubertal stage, and all were drug-naive. Circadian and sleep parameters were studied using an ambulatory circadian monitoring (ACM) device, and saliva samples were collected around the onset of sleep to determine dim light melatonin onset (DLMO). Results: Prepubertal individuals with ASD presented later DLMO and an earlier decline in melatonin during adolescence. A relationship was found between melatonin and both sleep and circadian parameters. Participants and controls with later DLMOs were more likely to have delayed sleep onset times. In the ASD group, subjects with the later daytime midpoint of temperature had a later DLMO. Later melatonin peak time and DLMO time were related to lower general motor activity and lower stability of its rhythms. Conclusion: The melatonin secretion pattern was different in individuals with ASD, and it showed a relationship with sleep and circadian parameters. Alterations in DLMO have not been previously reported in ASD with the exception of more variable DLMO timing; however, high variability in the study design and sample characteristics prevents direct comparison. The ACM device enabled the measurement of circadian rhythm, a scarcely described parameter in autistic children. When studied in combination with other measures such as melatonin, ACM can offer further knowledge on sleep problems in ASD.

Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children.

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6-8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables.

Sex-dependent relationship of C-reactive protein levels with HDL-cholesterol and HDL-phospholipid concentrations in children.

Obesity has been consistently associated with inflammation but the influence of HDL on this association remains under study. Our study analyzes the influence of obesity-related parameters in the relationship of high-sensitivity C-reactive protein (hs-CRP) with HDL-cholesterol and HDL-phospholipid in male and female adolescents. The study sample population comprised 350 males and 401 females aged 12 to 16 years. Information regarding anthropometric parameters, HDL-cholesterol, HDL-phospholipid, adiponectin, leptin, insulin, and hs-CRP concentrations was available. hs-CRP levels were inversely related to HDL-cholesterol and HDL-phospholipid in males but not in females, and were positively related to leptin concentrations in both sexes but were not related to adiponectin levels. In regression analyses, HDL-phospholipid and leptin appeared significantly associated to hs-CRP in males in a model explaining 14.3% of hs-CRP variation. In females, only leptin appeared related to hs-CRP concentrations. After adjusting by leptin and adiponectin, males in the highest hs-CRP tertile showed significantly lower levels of HDL-cholesterol and HDL-phospholipid than those in tertiles 1 and 2, while no significant differences in HDL-cholesterol and HDL-phospholipid concentrations by hs-CRP tertile were observed in females. In summary, high hs-CRP levels were associated with lower plasma HDL-cholesterol and HDL-phospholipid concentrations in male adolescents irrespective of adipokines, while in females, HDL-related parameters are not associated with hs-CRP concentrations.

Diagnostic yield of clinical exome sequencing in congenital hypogonadotropic hypogonadism considering the degree of olfactory impairment.

INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) can present alone or in association with anosmia or other congenital malformations. More than 30 genes have been identified as being involved in the pathogenesis of CHH with different patterns of inheritance, and the increasing availability of next generation sequencing (NGS) has increased the diagnostic yield. METHODS: We analysed the diagnostic yield of NGS in patients with CHH using the clinical exome filtered with virtual panels. We also assessed whether designing panels based on the presence/absence of microsmia increased the diagnostic yield. RESULTS: The use of a 34-gene virtual panel confirmed the diagnosis of CHH in 5 out of 9 patients (55%) patients. In 2 out of 9 (22%), the findings were inconclusive. Applying the presence/absence of microsmia criterion to choose genes for analysis did not improve the diagnostic yield. CONCLUSIONS: The approach to the genetic study of patients with CHH varies depending on the resources of each healthcare facility, so the sensitivity of testing may vary substantially depending on whether panels, clinical exome sequencing or whole exome sequencing (WES) are used. The analysis of all genes related to CHH regardless of the presence/absence of microsmia seems to be the best approach.

PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. Pharmacological activators of PPARγ are being used as a treatment of obesity related disorders such as dyslipidaemia and type 2 diabetes, but questions remain open regarding the effects of PPARγ on traits related to the development of type 2 diabetes. In our study, we have analyzed the relationship of the common variant Pro12Ala in the human PPARγ2 gene with the presence of obesity and with insulin, HOMA and lipid profile in a representative sample of 6-to 8-year-old children free from the confounding factors associated with adults. We found that Ala12Ala genotype was significantly more frequent in females with obesity than in those without obesity, with Ala12Ala carriers having significantly higher weight and body mass index (BMI), however the association disappeared when adjusting by leptin concentrations. The Ala12Ala genotype was associated with significantly higher HDL-cholesterol and apoA-I levels in males but not in females, independently of BMI. In a recessive model, in females, leptin levels appeared higher in Ala12Ala carriers. Although no apparent differences were observed in any sex when analyzing insulin levels and HOMA among genotypes without adjusting, lower insulin levels and lower HOMA appeared associated with Ala12Ala carriers when adjusting for BMI and leptin levels. In summary, our data showed that leptin seems to be having an effect on the association between the PPARγ2 Pro12Ala and BMI. Besides, after controlling for BMI and leptin, a protective effect of the Ala12Ala variant of the PPARγ2 Pro12Ala polymorphism on insulin sensitivity is evident already in prepubertal children.

Leptin Concentration, Obesity, and Plasma Non-esterified Fatty Acid Levels in Children.

The association between obesity and higher non-esterified fatty acid (NEFA) levels has been established in adults. In contrast, lower NEFA levels have been described in children with obesity although the reason behind this association remains unclear. Leptin, which regulates body weight and plays a role in lipolysis, could be involved in this relationship. We evaluated the influence of leptin in the association between obesity and NEFA concentrations in children, analyzing two cohorts including 684 6- to 8-year-olds and 836 12- to 16-year-old children, respectively. After adjusting by leptin, insulin levels remained significantly higher in adolescents with obesity as compared with levels in those without obesity. However, insulin levels showed no differences between prepubertal children with and without obesity. The significantly lower NEFA concentrations observed in 6- to 8-year-old girls with obesity disappeared when comparing NEFA levels between girls with and without obesity after adjusting by leptin. We report an influence of leptin levels on the association between obesity and insulin and NEFA in young children that is not observed in adolescents. Our findings add information about factors that may contribute to explain the lower NEFA levels described in prepubertal children with obesity.