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 1H‐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.
Ectopic fat deposition in liver and skeletal muscle tissue is related to cardiovascular disease risk and is a common metabolic complication in obese children. We evaluated the hypotheses of ectopic ...fat in these organs could be diminished following 1 year of multidisciplinary care specialized in childhood obesity, and whether this reduction would associate with changes in other markers of metabolic function.
This observational longitudinal study evaluated 40 overweight children and adolescents enrolled in a multidisciplinary treatment protocol at the Children's Obesity Clinic, Holbæk, Denmark. The participants were assessed by anthropometry, fasting blood samples (HbA1c, glucose, insulin, lipids, and biochemical variables of liver function), and liver and muscle fat content assessed by magnetic resonance spectroscopy at enrollment and following an average of 12.2 months of care. Univariate linear regression models adjusted for age, sex, treatment duration, baseline degree of obesity, and pubertal developmental stage were used for investigating possible associations.
The standard deviation score (SDS) of baseline median body mass index (BMI) was 2.80 (range: 1.49-3.85) and the median age was 14 years (10-17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage.
A 1-year multidisciplinary intervention program in the setting of a childhood obesity outpatient clinic confers a biologically important reduction in liver and muscle fat; metabolic improvements that are independent of the magnitude of concurrent weight loss.
ClinicalTrials.gov registration number: NCT00928473 , the Danish Childhood Obesity Biobank. Registered June 25, 2009.
The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex ...interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD) complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events), and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring.
•Ficolin1 plasma concentration is correlated wih disease activity in SLE patients.•Ficolin-1 plasma concentration is correlated with damage score and arterial thrombosis.•Function of the ficolin-3 ...pathway is associated with disease activity.•The ficolins may be involved in the pathohysiology of SLE.
The complement system plays a pathophysiological role in systemic lupus erythematosus (SLE). This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE.
EDTA plasma samples from 68 Danish SLE patients and 29 healthy donors were included in the study. Plasma concentrations of Ficolin-1, -2, and -3 were determined in specific sandwich ELISAs. Lectin pathway activity via Ficolin-3 was measured in ELISA on acetylated bovine serum albumin (acBSA) and measured as Ficolin-3 binding and deposition of C4, C3 and the terminal complement complex (TCC).
SLE patients had increased levels of Ficolin-3, 21.6μg/ml as compared to 17.0μg/ml in healthy controls (P=0.0098). The Ficolin-1 plasma concentration was negatively correlated with SLE Disease Activity Index (SLEDAI) (Rho=−0.29, P=0.015) and positively correlated to the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) (Rho=0.27, P=0.026). The Ficolin-1 concentration was also associated with the occurrence of arterial (P=0.0053) but not venous thrombosis (P=0.42). Finally, deposition of C4, C3 and TCC in the Ficolin-3 pathway were all correlated to SLEDAI, respectively (P<0.0076).
The Ficolin-1 association to SLEDAI and SDI as well as arterial thrombosis shown in this study suggests that Ficolin-1 may be a potential new biomarker for patients with SLE. Furthermore, Ficolin-3 mediated complement activation may be valuable in monitoring disease activity in SLE patients due to the high sensitivity for complement consumption in the assay independent of the Ficolin-3 concentration.
Sensory properties of some foods may be of importance to energy consumption and thus the development and maintenance of childhood obesity. This study compares selected food related qualities in ...overweight and normal weight children. Ninety-two participants were included; 55 were overweight with a mean age of 11.6 years (range 6–18 years) and a mean BMI z-score of 2.71 (range 1.29–4.60). The 37 normal weight children had a mean age of 13.0 years (range 6–19 years) and a mean BMI z-score of 0.16 (range −1.71 to 1.24). All children completed a half-hour long meal test consisting of alternation between consumption of foods and answering of questionnaires. Compared to the normal weight, the overweight children displayed lower self-reported intake paces (χ2(2) = 6.3, p = 0.04), higher changes in liking for mozzarella (F(1,63) = 9.55, p = 0.003) and pretzels (F(1,87) = 5.27, p = 0.024), and declines in wanting for something fat, of which the normal weight children displayed an increase (F(1,83) = 4,10, p = 0.046). No differences were found for sensory-specific satiety, wanting for the main food yoghurt, hunger, or satiety. In conclusion, overweight children did not differ from normal weight children in terms of sensory-specific satiety, hunger, or satiety. However, overweight children had lower intake paces and appeared to differ from normal weight children regarding foods with a fatty taste.
•All children displayed SSS independent of BMI z-score.•All children displayed declines in wanting independent of BMI z-score.•The perception of fat foods may be dependent on BMI z-score.•The overweight children reported a faster intake pace compared to the normal weight children.
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