Genetics of Plasma Bilirubin and Associations between Bilirubin and Cardiometabolic Risk Profiles in Danish Children and Adolescents.

Bilirubin is the end product of heme catabolism, mainly produced by the breakdown of mature red blood cells. Due to its anti-inflammatory, antioxidant, antidiabetic, and antilipemic properties, circulating bilirubin concentrations are inversely associated with the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality in adults. Some genetic loci associated with circulating bilirubin concentrations have been identified by genome-wide association studies in adults. We aimed to examine the relationship between circulating bilirubin, cardiometabolic risk factors, and inflammation in children and adolescents and the genetic architecture of plasma bilirubin concentrations. We measured fasting plasma bilirubin, cardiometabolic risk factors, and inflammatory markers in a sample of Danish children and adolescents with overweight or obesity (n = 1530) and in a population-based sample (n = 1820) of Danish children and adolescents. Linear and logistic regression analyses were performed to analyze the associations between bilirubin, cardiometabolic risk factors, and inflammatory markers. A genome-wide association study (GWAS) of fasting plasma concentrations of bilirubin was performed in children and adolescents with overweight or obesity and in a population-based sample. Bilirubin is associated inversely and significantly with a number of cardiometabolic risk factors, including body mass index (BMI) standard deviation scores (SDS), waist circumference, high-sensitivity C-reactive protein (hs-CRP), homeostatic model assessment for insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), triglycerides, and the majority of measured inflammatory markers. In contrast, bilirubin was positively associated with fasting plasma concentrations of alanine transaminase (ALT), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SDS), and the inflammatory markers GH, PTX3, THBS2, TNFRSF9, PGF, PAPPA, GT, CCL23, CX3CL1, SCF, and TRANCE. The GWAS showed that two loci were positively associated with plasma bilirubin concentrations at a p-value threshold of <5 × 10-8 (rs76999922: ß = -0.65 SD; p = 4.3 × 10-8, and rs887829: ß = 0.78 SD; p = 2.9 × 10-247). Approximately 25% of the variance in plasma bilirubin concentration was explained by rs887829. The rs887829 was not significantly associated with any of the mentioned cardiometabolic risk factors except for hs-CRP. Our findings suggest that plasma concentrations of bilirubin non-causally associates with cardiometabolic risk factors in children and adolescents.

An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents.

BACKGROUND & AIMS: Genome-wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome-wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents. APPROACH & RESULTS: Children and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population-based group (n = 1890) were included. Cardiometabolic risk outcomes and genotypes were obtained. Liver fat was quantified using 1 H-MRS in a subset of 727 participants. Variants in PNPLA3, TM6SF2, GPAM and TRIB1 were associated with higher liver fat (p < .05) and with distinct patterns of plasma lipids. The GRS was associated with higher liver fat content, plasma concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST) and favourable plasma lipid levels. The GRS was associated with higher prevalence of hepatic steatosis (defined as liver fat ≥5.0%) (odds ratio per 1-SD unit: 2.17, p = 9.7E-10). A prediction model for hepatic steatosis including GRS alone yielded an area under the curve (AUC) of 0.78 (95% CI 0.76-0.81). Combining the GRS with clinical measures (waist-to-height ratio [WHtR] SDS, ALT, and HOMA-IR) increased the AUC up to 0.86 (95% CI 0.84-0.88). CONCLUSIONS: The genetic predisposition for liver fat accumulation conferred risk of hepatic steatosis in children and adolescents. The liver fat GRS has potential clinical utility for risk stratification.

High Plasma Levels of Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 Are Associated With Inflammation and Cardiometabolic Risk Profiles in Pediatric Overweight and Obesity.

Background Lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 is a scavenger receptor for oxidized low-density lipoprotein. In adults, higher soluble lectin-like ox-LDL receptor-1 (sLOX-1) levels are associated with cardiovascular disease, type 2 diabetes, and obesity, but a similar link in pediatric overweight/obesity remains uncertain. Methods and Results Analyses were based on the cross-sectional HOLBAEK Study, including 4- to 19-year-olds from an obesity clinic group with body mass index >90th percentile (n=1815) and from a population-based group (n=2039). Fasting plasma levels of sLOX-1 and inflammatory markers were quantified, cardiometabolic risk profiles were assessed, and linear and logistic regression analyses were performed. Pubertal/postpubertal children and adolescents from the obesity clinic group exhibited higher sLOX-1 levels compared with the population (P<0.001). sLOX-1 positively associated with proinflammatory cytokines, matrix metalloproteinases, body mass index SD score, waist SD score, body fat %, plasma alanine aminotransferase, serum high-sensitivity C-reactive protein, plasma low-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure SD score, and inversely associated with plasma high-density lipoprotein cholesterol (all P<0.05). sLOX-1 positively associated with high alanine aminotransferase (odds ratio [OR], 1.16, P=4.1 E-04), insulin resistance (OR, 1.16, P=8.6 E-04), dyslipidemia (OR, 1.25, P=1.8 E-07), and hypertension (OR, 1.12, P=0.02). Conclusions sLOX-1 levels were elevated during and after puberty in children and adolescents with overweight/obesity compared with population-based peers and associated with inflammatory markers and worsened cardiometabolic risk profiles. sLOX-1 may serve as an early marker of cardiometabolic risk and inflammation in pediatric overweight/obesity. Registration The HOLBAEK Study, formerly known as The Danish Childhood Obesity Biobank, ClinicalTrials.gov identifier number NCT00928473, https://clinicaltrials.gov/ct2/show/NCT00928473 (registered June 2009).

Hyperglucagonemia in Pediatric Adiposity Associates With Cardiometabolic Risk Factors but Not Hyperglycemia.

CONTEXT: In adults, hyperglucagonemia is associated with type 2 diabetes, impaired glucose tolerance, and obesity. The role of glucagon in pediatric overweight/obesity remains unclear. OBJECTIVE: We examined whether fasting concentrations of glucagon are elevated in youth with overweight/obesity and whether this associates with cardiometabolic risk profiles. METHODS: Analyses were based on the cross-sectional HOLBAEK study, including children and adolescents 6 to 19 years of age, with overweight/obesity from an obesity clinic group (n = 2154) and with normal weight from a population-based group (n = 1858). Fasting concentrations of plasma glucagon and cardiometabolic risk outcomes were assessed, and multiple linear and logistic regressions models were performed. RESULTS: The obesity clinic group had higher glucagon concentrations than the population-based group (P < 0.001). Glucagon positively associated with body mass index (BMI) standard deviation score (SDS), waist, body fat %, liver fat %, alanine transaminase (ALT), high-sensitivity C-reactive protein, homeostasis model assessment of insulin resistance, insulin, C-peptide, LDL-C, triglycerides, SDS of diastolic and systolic blood pressure, and was inversely associated with fasting glucose. The inverse relationship between glucagon and glucose was attenuated in individuals with high BMI SDS and high fasting insulin. Glucagon was associated with a higher prevalence of insulin resistance, increased ALT, dyslipidemia, and hypertension, but not with hyperglycemia. Glucagon was positively associated with fasting total glucagon-like peptide-1. CONCLUSION: Compared with normal weight peers, children and adolescents with overweight/obesity had elevated concentrations of fasting glucagon, which corresponded to worsened cardiometabolic risk outcomes, except for hyperglycemia. This suggests hyperglucagonemia in youth may precede impairments in glucose regulation.

The Effect of Overweight and Obesity on Liver Biochemical Markers in Children and Adolescents.

BACKGROUND: Elevated plasma concentrations of liver enzymes are routinely used as markers of liver injury in adults and children. Currently, the age- and sex-specific effects of adiposity on pediatric liver enzyme concentrations are unclear. METHODS: We included participants from 2 cohorts of Danish children and adolescents: 1858 from a population-based cohort and 2155 with overweight or obesity, aged from 6 to 18 years. Age- and sex-specific percentile curves were calculated for fasting plasma concentrations of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP) in both cohorts. Hepatic fat content was assessed by proton magnetic resonance spectroscopy in 458 participants. RESULTS: Concentrations of ALT, AST, LDH, and ALP decreased with age in both girls and boys, while GGT and bilirubin were comparable across age groups in girls and increased slightly with age in boys. Children and adolescents with overweight or obesity exhibited higher concentrations of ALT in all age groups. Concentrations of ALT, and to a lesser degree GGT, increased with age in boys with overweight or obesity. Optimal ALT cut-points for diagnosing hepatic steatosis (liver fat content > 5%) was 24.5 U/L for girls (sensitivity: 55.6%, specificity: 84.0%), and 34.5 U/L for boys (sensitivity: 83.7%, specificity: 68.2%). CONCLUSIONS: Pediatric normal values of liver enzymes vary with both age and sex. Overweight and obesity is associated with elevated biochemical markers of liver damage. These findings emphasize the need for prevention and treatment of overweight and obesity in children and adolescents. (J Clin Endocrinol Metab XX: 0-0, 2019).

Hidradenitis suppurativa in a cohort of overweight and obese children and adolescents.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recurring disease mainly observed in adults. Obesity is considered an important independent factor in HS development and is associated with a higher prevalence of HS in children. We aimed to characterize the clinical presentation of HS in overweight and obese children and adolescents. METHODS: We performed a cross-sectional observational study during January 2007-April 2015. Overweight and obese patients (5-17 years of age, BMI> 90th percentile) referred to The Children's Obesity Clinic, Department of Paediatrics, Copenhagen University Hospital Holbaek, Denmark, underwent screening for dermatological conditions. A dermatologist ascertained the diagnosis of HS, and disease severity was assessed using Hurley staging and Sartorius score. Tobacco smoke exposure, body mass index (BMI) standard deviation score (SDS), and psychiatric comorbidities were recorded. Our cohort was compared with a reference cohort recruited in a previous study. RESULTS: A total of 195 children and adolescents underwent screening for dermatological conditions. Nine patients screened positive, and six of these patients were available for examination of whom five presented with HS. All HS cases were mild (median Sartorius score of 9). Four of the five patients (with varying constellations) reported tobacco exposure, a positive family history of HS, and exhibited psychiatric comorbidities. CONCLUSION: Our findings support that the presence of pediatric HS is correlated with familial disposition to HS and psychiatric comorbidities.

Abdominal adiposity and cardiometabolic risk factors in children and adolescents: a Mendelian randomization analysis.

BACKGROUND: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear. OBJECTIVE: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization. METHODS: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y. RESULTS: WHRadjBMI GRS was associated with higher WHRadjBMI (ß = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: ß = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: ß = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: ß = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (ß = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (ß = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal. CONCLUSIONS: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.

Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents.

BACKGROUND: Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children. METHODS: We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist-hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3-18 years. RESULTS: The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHRadjBMI beta = -0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = -0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01-1.13, P = 0.012, n = 536). CONCLUSIONS: Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.

Glucose metabolism in children and adolescents: Population-based reference values and comparisons to children and adolescents enrolled in obesity treatment.

BACKGROUND: Alterations in glucose metabolism that lead to the development of metabolic and cardiovascular disease may begin already in childhood. OBJECTIVE: This study aims to generate pediatric age and sex-specific reference values for fasting concentrations of glucose, hemoglobin A1c (HbA1c), insulin, C-peptide, and homeostasis model assessment: insulin resistance (HOMA-IR) in Danish/North-European white children and adolescents from a population-based cohort and to compare values from children and adolescents with overweight/obesity with this reference. METHODS: The population- and obesity clinic-based cohorts consisted of 2451 and 1935 children and adolescents between 6 and 18 years of age. Anthropometric measurements and blood samples were obtained and percentile curves were calculated. RESULTS: In the population-based cohort, glucose, insulin, and HOMA-IR values increased before the expected onset of puberty (P < .05). Thereafter, all variables decreased in girls (P < .05) and HbA1c decreased in boys (P < .05). Concentrations of all measured markers of glucose metabolism were higher in the obesity clinic-based cohort than the population-based cohort (both sexes P < .001). Specifically, insulin and HOMA-IR continued to increase to 18 years in the clinic-based cohort, particularly among boys. CONCLUSIONS: Fasting glucose, insulin, and HOMA-IR change during childhood, making pediatric reference values essential for timely identification of derangements in glucose metabolism. Children and adolescents with obesity exhibit increased concentrations of these biomarkers.

Impaired fasting glucose and the metabolic profile in Danish children and adolescents with normal weight, overweight, or obesity.

OBJECTIVE: Whether the definitions of impaired fasting glucose (IFG) from the American Diabetes Association (ADA) and the World Health Organization (WHO) differentially impact estimates of the metabolic profile and IFG-related comorbidities in Danish children and adolescents is unknown. METHODS: Two thousand one hundred and fifty four (979 boys) children and adolescents with overweight or obesity (median age 12 years) and 1824 (728 boys) children with normal weight (median age 12 years) from The Danish Childhood Obesity Biobank were studied. Anthropometrics, blood pressure, puberty, and fasting concentrations of glucose, insulin, glycosylated hemoglobin (HbA1c), and lipids were measured. RESULTS: About 14.1% of participants with overweight or obesity exhibited IFG according to the ADA and 3.5% according to the WHO definition. Among individuals with normal weight, the corresponding prevalences were 4.3% and 0.3%. IFG was associated with a higher systolic blood pressure, higher concentrations of HbA1c, insulin, C-peptide (P < .0001) and triglycerides (P = .03), and lower HOMA2-IS and HOMA2-B (P < .0001) independent of sex, age, puberty, waist-to-height ratio, and degree of obesity. Furthermore, IFG was associated with a higher risk for hypertension (OR = 1.66 [95%CI: 1.21; 2.28], P = .002) and dyslipidemia (OR = 1.90 [95%CI: 1.38; 2.56], P < .0001) compared with the group without IFG independent of age, sex, and puberty. CONCLUSIONS: The prevalence of IFG, when applying the ADA criterion compared with the WHO criterion, was 4 times higher in individuals with overweight and obesity and 14 times higher in individuals with normal weight in this study sample of children and adolescents. IFG was associated with a higher risk of hypertension and dyslipidemia compared with their normoglycemic peers regardless of the definition applied.

The effect of impaired glucose metabolism on weight loss in multidisciplinary childhood obesity treatment.

OBJECTIVE: To investigate whether children and adolescents exhibiting an impaired glucose metabolism are more obese at treatment entry and less likely to reduce their degree of obesity during treatment. METHODS: The present study is a longitudinal observational study, including children and adolescents from the Children's Obesity Clinic, Holbaek, Denmark. Anthropometrics, pubertal development, socioeconomic status (SES), and fasting concentrations of plasma glucose, serum insulin, serum C-peptide, and whole blood glycosylated hemoglobin (HbA1c) were collected at treatment entry and at follow-up. Proxies of Homeostasis Model Assessment 2-insulin sensitivity (HOMA2-IS) and Homeostasis Model Assessment 2-ß-cell function (HOMA2-B) were calculated with the Homeostasis Model Assessment 2 program. RESULTS: In total, 569 (333 boys) patients, median 11.5 years of age (range 6-22 years), and median body mass index (BMI) z-score 2.94 (range 1.34-5.54) were included. The mean BMI z-score reduction was 0.31 (±0.46) after 13 months (range 6-18) of treatment. At treatment entry, patients with impaired estimates of glucose metabolism were more obese than normoglycemic patients. Baseline concentration of C-peptide was associated with a lower weight loss during treatment in girls (P = .02). Reduction in the insulin concentrations was associated with reduction in BMI z-score in both sexes (P < .0001, P = .0005). During treatment, values of glucose, HbA1c, HOMA2-IS, and HOMA2-B did not change or impact the treatment outcome, regardless of age, sex, SES, or degree of obesity at treatment entry. CONCLUSION: The capability to reduce weight during multidisciplinary treatment in children and adolescents with overweight/obesity is not influenced by an impaired glucose metabolism at study entry or during the course of treatment.

Self-Reported Versus Accelerometer-Assessed Daily Physical Activity in Childhood Obesity Treatment.

We investigated the relationship between interview-based subjective ratings of physical activity (PA) engagement and accelerometer-assessed objectively measured PA in children and adolescents with overweight or obesity. A total of 92 children and adolescents (40 males, 52 females) with BMI ≥ 90th percentile for sex and age, aged 5-17 years had valid GT3X + accelerometer-assessed PA and interview-assessed self-reported information on PA engagement at the time of enrollment in a multidisciplinary outpatient tertiary treatment for childhood obesity. Accelerometer-derived mean overall PA and time spent in moderate to vigorous physical intensity were generated, applying cut-offs based on Vector Magnitude settings as defined by Romanzini et al. (2014), and a physical activity score (PAS) based on self-reported data. Overall, a higher self-reported PAS was correlated with higher accelerometer-assessed daily total PA levels ( r = 0.34, p < .01) and children who reported a high PAS were more physically active compared with children who reported a low PAS. There was a fair level of agreement between self-reported PAS and accelerometer-assessed PA (Kappa agreement = 0.23; 95% CI = [0.03, 0.43]; p = .01). PAS, derived from self-report, may be a useful instrument for evaluating PA at a group level among children and adolescents enrolled in multidisciplinary obesity treatment.

Effects of a Family-Based Childhood Obesity Treatment Program on Parental Weight Status.

OBJECTIVE: The aim of this study was to investigate the prevalence of overweight/obesity among parents of children entering childhood obesity treatment and to evaluate changes in the parents' weight statuses during their child's treatment. METHODS: The study included parents of 1,125 children and adolescents aged 3-22 years, who were enrolled in a multidisciplinary childhood obesity treatment program. At baseline, weight and height of the parents were obtained by self-reported information and parental body mass index (BMI) was calculated. Weight and height of the children were measured in the clinic and BMI standard deviation scores were calculated. Furthermore, anthropometric data from parents of 664 children were obtained by telephone interview after a mean of 2.5 years of treatment (ranging 16 days to 7 years), and changes in parental BMI were analyzed. RESULTS: Data on changes in BMI were available in 606 mothers and 479 fathers. At baseline, the median BMI of the mothers was 28.1 kg/m2 (range: 16.9-66.6), and the median BMI of the fathers was 28.9 kg/m2 (range: 17.2-48.1). Seventy percent of the mothers and 80% of the fathers were overweight or obese at the time of their child's treatment initiation. Both the mothers and fathers lost weight during their child's treatment with a mean decrease in BMI in the mothers of 0.5 (95% CI: 0.2-0.8, p = 0.0006) and in the fathers of 0.4 (95% CI: 0.2-0.6, p = 0.0007). Of the overweight/obese parents, 60% of the mothers and 58% of the fathers lost weight during their child's treatment. CONCLUSION: There is a high prevalence of overweight/obesity among parents of children entering childhood obesity treatment. Family-based childhood obesity treatment with a focus on the child has a positive effect on parental BMI with both mothers and fathers losing weight. TRIAL REGISTRATION: ClinicalTrials.gov NCT00928473.

Muscle fat content and abdominal adipose tissue distribution investigated by magnetic resonance spectroscopy and imaging in obese children and youths.

The degree of fat deposition in muscle and its implications for obesity-related complications in children and youths are not well understood. One hundred and fifty-nine patients (mean age: 13.3 years; range: 6-20) with a body mass index (BMI) >90(th) percentile for age and sex were included. Muscle fat content (MFC) was measured in the psoas muscle by proton magnetic resonance spectroscopy. The patients were assigned to two groups: MFC <5% or ≥5%. Visceral adipose tissue volume (VAT) and subcutaneous adipose tissue volume (SAT) were measured by magnetic resonance imaging. The data were analysed to detect associations between MFC and BMI standard deviation scores, VAT and SAT, blood values, pubertal stages, and physical activity scores. The mean BMI standard deviation score (SDS) was 3.04 (range 1.32-5.02). The mean MFC was 8.9% (range 0.8-46.7), and 118 (74.2%) of 159 patients had an MFC ≥5%. Children with an MFC ≥5%, compared with children with an MFC <5%, had a higher BMI SDS (P=0.03), a higher VAT (P=0.04), and elevated intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) contents (both P<0.0001). SAT, SAT/VAT ratio, blood values, pubertal stages and physical activity scores did not differ between the two groups. Severely obese children and youths tend to have a high MFC, which is associated with elevated VAT, IMCL, and EMCL contents. An increased MFC may be associated with impaired metabolic processes, which may predispose these young people to obesity-related complications.