Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children.

Altered gut microbiota and metabolites are important for non-alcoholic fatty liver disease (NAFLD) in children. We aimed to comprehensively examine the effects of gut metabolites on NAFLD progression. We performed integrative metabolomics (untargeted discovery and targeted validation) analysis of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and obesity in children. Fecal samples were collected from 75 subjects in the discovery cohort (25 NAFL, 25 NASH, and 25 obese control children) and 145 subjects in an independent validation cohort (53 NAFL, 39 NASH, and 53 obese control children). Among 2,491 metabolites, untargeted metabolomics revealed a complete NAFLD metabolic map containing 318 increased and 123 decreased metabolites. Then, machine learning selected 65 important metabolites that can distinguish the severity of the NAFLD. Furthermore, precision-targeted metabolomics selected 5 novel gut metabolites from 20 typical metabolites. The functionality of candidate metabolites was validated in hepatocyte cell lines. In the end, this study annotated two novel elevated pathogenic metabolites (dodecanoic acid and creatinine) and a relationship between depleted protective gut microbiota (Butyricicoccus and Alistipes), increased inflammation (IL-1ß), lipid metabolism (TG), and liver function (ALT and AST). This study demonstrates the role of novel gut metabolites (dodecanoic acid and creatinine), as the fatty acid metabolism regulator contributing to NAFLD development through its influence on inflammation and liver function. IMPORTANCE: Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (Butyricicoccus and Alistipes) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.

Associations of infant feeding practices with abdominal and hepatic fat measures in childhood in the longitudinal Healthy Start Study.

BACKGROUND: Infant feeding patterns have been linked with obesity risk in childhood, but associations with precise measures of body fat distribution are unclear. OBJECTIVE: We examined associations of infant feeding practices with abdominal fat and hepatic fat trajectories in childhood. METHODS: This study included 356 children in the Healthy Start Study, a prospective prebirth cohort in Colorado. Infant feeding practices were assessed by postnatal interviews and categorized as any human milk <6 mo compared with ≥6 mo; complementary foods introduced ≤4 mo compared with >4 mo; soda introduced ≤18 mo compared with >18 mo. Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) areas and hepatic fat (%) were assessed by magnetic resonance imaging in early and middle childhood (median 5 and 9 y old, respectively). We examined associations of infant feeding with adiposity trajectories across childhood using linear mixed models. RESULTS: In the sample of children, 67% consumed human milk ≥6 mo, 75% were introduced to complementary foods at >4 mo, and 81% were introduced to soda at >18 mo. We did not find any associations between duration of any human milk consumption and childhood adiposity trajectories. Early introduction to complementary foods (≤4 mo) was associated with faster rates of change for SAT and VAT during childhood (Slope [95% CI]: 15.1 [10.7,19.4] cm2/y for SAT; 2.5 [1.9,2.9] cm2/y for VAT), compared with introduction at >4 mo (5.5 [3.0,8.0] cm2/y and 1.6 [1.3,1.9] cm2/y, respectively). Similarly, early introduction to soda (≤18 mo) was associated with faster rates of change for all 3 outcomes during childhood (Slope [95% CI]: 20.6 [15.0,26.1] cm2/y for SAT, 2.7 [2.0,3.3] cm2/y for VAT, 0.3 [0.1,0.5] %/year for hepatic fat) compared with delayed introduction (5.4 [2.8,8.0] cm2/y, 1.7 [1.3, 2.0] cm2/y, -0.1 [-0.2,0.0] %/y, respectively). CONCLUSIONS: The timing of introduction and quality of complementary foods in infancy was associated with rates of abdominal and hepatic fat accrual during childhood. Experimental studies are needed to assess underlying mechanisms.

Overweight/Obesity-related microstructural alterations of the fimbria-fornix in the ABCD study: The role of aerobic physical activity.

Childhood overweight/obesity has been associated with negative consequences related to brain function and may involve alterations in white matter pathways important for cognitive and emotional processing. Aerobic physical activity is a promising lifestyle factor that could restore white matter alterations. However, little is known about either regional white matter alterations in children with overweight/obesity or the effects of aerobic physical activity targeting the obesity-related brain alterations in children. Using a large-scale cross-sectional population-based dataset of US children aged 9 to 10 years (n = 8019), this study explored the associations between overweight/obesity and microstructure of limbic white matter tracts, and examined whether aerobic physical activity may reduce the overweight/obesity-related white matter alterations in children. The primary outcome measure was restriction spectrum imaging (RSI)-derived white matter microstructural integrity measures. The number of days in a week that children engaged in aerobic physical activity for at least 60 minutes per day was assessed. We found that females with overweight/obesity had lower measures of integrity of the fimbria-fornix, a major limbic-hippocampal white matter tract, than their lean peers, while this difference was not significant in males. We also found a positive relationship between the number of days of aerobic physical activity completed in a week and integrity measures of the fimbria-fornix in females with overweight/obesity. Our results provide cross-sectional evidence of sex-specific microstructural alteration in the fimbria-fornix in children with overweight/obesity and suggest that aerobic physical activity may play a role in reducing this alteration. Future work should examine the causal direction of the relationship between childhood overweight/obesity and brain alterations and evaluate potential interventions to validate the effects of aerobic physical activity on this relationship.

Obesity-induced thymic involution and cancer risk.

Declining thymic functions associated either with old age (i.e., age-related thymic involution), or with acute involution as a result of stress, infectious disease, or cytoreductive therapies (e.g., chemotherapy/radiotherapy), have been associated with cancer development. A key mechanism underlying such increased cancer risk is the thymus-dependent debilitation of adaptive immunity, which is responsible for orchestrating immunoediting mechanisms and tumor immune surveillance. In the past few years, a blooming set of evidence has intriguingly linked obesity with cancer development and progression. The majority of such studies has focused on obesity-driven chronic inflammation, steroid/sex hormone and adipokine production, and hyperinsulinemia, as principal factors affecting the tumor microenvironment and driving the development of primary malignancy. However, experimental observations about the negative impact of obesity on T cell development and maturation have existed for more than half a century. Here, we critically discuss the molecular and cellular mechanisms of obesity-driven thymic involution as a previously underrepresented intermediary pathology leading to cancer development and progression. This knowledge could be especially relevant in the context of childhood obesity, because impaired thymic function in young individuals leads to immune system abnormalities, and predisposes to various pediatric cancers. A thorough understanding behind the molecular and cellular circuitries governing obesity-induced thymic involution could therefore help towards the rationalized development of targeted thymic regeneration strategies for obese individuals at high risk of cancer development.

[Cerebral perfusion and tractography in obese children]. / Rezul'taty izucheniya tserebral'noi perfuzii i traktografii u detei s ozhireniem.

OBJECTIVE: To study the relationship of the structure of the white matter of the brain, neurovascularization and cognitive functions in obese children and adolescents. MATERIAL AND METHODS: The study included 64 obese patients, aged 12-17 years, and 54 children without excess body weight. A general clinical examination, neuropsychological testing (the Raven's test with the calculation of IQ, MoCA, the Rey 15-Item Memory Test (RMT), 1 and 2), magnetic resonance imaging (MR) tractography and contrast-free perfusion of the brain were conducted. RESULTS: Obese children and adolescents had both a decrease in scores on MoCA and the Raven's test, and in terms of IQ, while according to RMT-1, there were significant differences in the two groups, and in RMT-2 the results were comparable. Perfusion analysis showed a decrease in vascularization in the white matter area of the occipital lobe on the left and its increase in the temporal lobe area also on the left. When assessing the white matter according to MR tractography, a decrease in fractional anisotropy was noted in the area of the hook-shaped beam on the right and left, anterior and posterior commissural tracts. These changes were correlated with neuropsychological results. CONCLUSION: In obese children and adolescents, there was a destruction of the integrity of the white matter and neurovascularization of the brain associated with a deficit of cognitive functions.

EUS-guided fine-needle liver biopsy in pediatric patients using a modified technique with one-pass, one-actuation wet suction

Background and aims: liver biopsy (LB) can be a valuabletool to determine the etiology of pediatric liver disease.There is limited data on the role of EUS-LB in children. Thisstudy evaluated the efficacy and safety of a modified technique —(M)LB— in cases at high risk of bleeding or in obesechildren. In addition, the tissue yield of EUS-(M)LB and thepercutaneous (PC) approach were compared.Methods: a retrospective analysis was performed comparing EUS-(M)LB and PC-LB in children at a tertiary referral center. All consecutive children referred for PC-LB andEUS-LB who had an unexplained liver test abnormality afterexclusion of biliary disorders from March 2017 to August2018 were included. EUS-(M)LB consisted of a one pass wetsuction technique using a 19-gauge core needle. A comparison was performed between total specimen length (TSL)and number of complete portal triads (CPTs).Results: the cohort included 28 EUS-(M)LB and 28 PC-LBpediatric cases. Median (IQR) age was 14.5 years (13.4-16). Median TSL was 8.6 (5.8-9.6) in EUS-(M)LB cases and7 cm (7-9) in PC-LB cases (p = 0.788). The maximum intactspecimen was 2.8 cm (EUS-(M)LB) and 1.6 cm (PC-LB) (p= 0.009). The mean (SD) number of CPTs per sample was28.2 (7.3) and 11.6 (2.1), respectively (p = 0.001). Adverseevents included one case of self-limited abdominal pain inthe PC-LB group.Conclusion: EUS-(M)LB has the potential to be a safe andeffective alternative diagnostic modality, when compared toPC-LB, to evaluate children with unexplained liver test abnormalities who undergo EUS to evaluate biliary disorders. (AU)

Pathogenic effects of Desulfovibrio in the gut on fatty liver in diet-induced obese mice and children with obesity.

BACKGROUND: Although we know the key role of gut dysbiosis in nonalcoholic fatty liver disease (NAFLD), it remains unclear what microbe(s) are responsible. This study aims to identify the microbes that cause NAFLD. METHODS: C57BL/6JNarl male mice fed a high-fat diet (HFD) were orally administered Lactobacillus reuteri (L. reuteri) or Lactobacillus rhamnosus GG plus Bifidobacterium animalis subsp. lactis BB12 (LGG plus BB12). Their fecal microbiomes identified by 16S rRNA sequencing were correlated with the severity of fatty liver. We then used a human cohort to confirm the role of the microbe(s). The HFD-fed mice were administrated with the identified bacterium, Desulfovibrio. The histopathological changes in the liver and ileum were analyzed. RESULTS: Lactobacillus and Bifidobacterium improved hepatic steatosis and fibrosis in HFD-fed mice, which was related to the decreased abundance of Desulfovibrio in feces. Further human study confirmed the amount of D. piger in the fecal microbiota of obese children with NAFLD was increased. We then administered D. piger and found aggravated hepatic steatosis and fibrosis in HFD-fed mice. Hepatic expression of CD36 was significantly increased in HFD-fed mice gavaged with D. piger. In HepG2 cells, overexpression of CD36 increased lipid droplets, whereas knockdown of CD36 decreased lipid droplets. HFD-fed mice gavaged with D. piger had a decrease in the villus length, crypt depth, and zonula occludens-1 density in the ileum tissue. CONCLUSIONS: Our findings provide novel insights into the role of Desulfovibrio dysregulation in NAFLD. Modulation of Desulfovibrio may be a potential target for the treatment of NAFLD.

Controlled attenuation parameter in the diagnosis of different liver steatosis groups in children with obesity.

OBJECTIVE: To investigate the utility of the controlled attenuation parameter (CAP), as measured by a liver elastography technique, in predicting varying degrees of liver steatosis in children with obesity. METHODS: Children with obesity attending the pediatric obesity clinic at the Affiliated Hospital of Hangzhou Normal University from July 2020 to May 2021 were retrospectively analysed. The 71 subjects were divided into four groups according to the degree of liver steatosis obtained by magnetic resonance imaging-proton density fat fraction (MRI-PDFF). The gender, age, CAP, LSM, ALT, AST, BMI, uric acid, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, insulin, and blood 25-hydroxyvitamin D levels of the four groups were compared, and the differences were analysed. Clinical data with significant differences were included in the logistic regression analysis. The receiver operating characteristic (ROC) curve for the CAP for the 71 subjects with different degrees of liver steatosis was plotted to evaluate the diagnostic value. RESULTS: The 71 children were divided into groups according to the degree of hepatic steatosis obtained by MRI-PDFF, and the clinical data for each group were compared. It was found that there was statistical significance for CAP, ALT, and AST in cases of moderate and severe hepatic steatosis (p < 0.05). Logistic regression analysis was conducted between CAP, ALT, AST, and moderate to severe hepatic steatosis in children with obesity, and it was found that CAP was a factor related to moderate to severe hepatic steatosis in children with obesity. The ROC curve indicated that CAP has diagnostic value for NAFLD in children with obesity. CONCLUSION: There is diagnostic value in the use of CAP for hepatic steatosis in children with obesity, and there is greater diagnostic value in the use of CAP for children with moderate to severe hepatic steatosis.

EUS-guided fine-needle liver biopsy in pediatric patients using a modified technique with one-pass, one-actuation wet suction.

BACKGROUND AND AIMS: Liver biopsy (LB) can be a valuable tool to determine the etiology of pediatric liver disease. There is limited data of the role of EUS-LB in children. This study evaluated the efficacy and the safety of a modified technique (M)LB in cases at high risk of bleeding or obese children. In addition, the tissue yield of EUS-(M)LB and percutaneous (PC) approach were compared. METHODS: A retrospective analysis was performed, comparing EUS-(M)LB and PC-LB in children at a tertiary referral center. All consecutive children referred for PC-LB and EUS-LB who had an unexplained liver test abnormality after exclusion of biliary disorders from March-2017 to August-2018 were included. EUS-(M)LB consisted of a one pass wet suction technique using a 19-gauche core needle. A comparison was performed between total specimen length (TSL) and the number of complete portal triads (CPTs). RESULTS: The cohort included 28 EUS-(M)LB and 28 PC-LB pediatric cases. The median (IQR) age was 14.5 years (13.4-16). The median TSL was 8.6 (5.8-9.6) in EUS-(M)LB cases and 7 cm (7-9) in PC-LB cases (P =0.788). The maximum intact specimen was 2.8 cm (EUS-(M)LB) and 1.6 cm (PC-LB) (P =0.009). The mean (SD) number of CPTs per sample was 28.2 (7.3) and 11.6 (2.1), respectively (P =0.001). Adverse events included once case of self-limited abdominal pain in the PC-LB group. CONCLUSION: EUS-(M)LB has the potential to be a safe and effective alternative diagnostic modality when compared to PC-LB, to evaluate children with unexplained liver test abnormalities who undergo EUS to evaluate biliary disorders.

A three-dimensional atlas of child's cardiac anatomy and the unique morphological alterations associated with obesity.

AIMS: Statistical shape models (SSMs) of cardiac anatomy provide a new approach for analysis of cardiac anatomy. In adults, specific cardiac morphologies associate with cardiovascular risk factors and early disease stages. However, the relationships between morphology and risk factors in children remain unknown. We propose an SSM of the paediatric left ventricle to describe its morphological variability, examine its relationship with biometric parameters and identify adverse anatomical remodelling associated with obesity. METHODS AND RESULTS: This cohort includes 2631 children (age 10.2 ± 0.6 years), mostly Western European (68.3%) with a balanced sex distribution (51.3% girls) from Generation R study. Cardiac magnetic resonance short-axis cine scans were segmented. Three-dimensional left ventricular (LV) meshes are automatically fitted to the segmentations to reconstruct the anatomies. We analyse the relationships between the LV anatomical features and participants' body surface area (BSA), age, and sex, and search for features uniquely related to obesity based on body mass index (BMI). In the SSM, 19 modes described over 90% of the population's LV shape variability. Main modes of variation were related to cardiac size, sphericity, and apical tilting. BSA, age, and sex were mostly correlated with modes describing LV size and sphericity. The modes correlated uniquely with BMI suggested that obese children present with septo-lateral tilting (R2 = 4.0%), compression in the antero-posterior direction (R2 = 3.3%), and decreased eccentricity (R2 = 2.0%). CONCLUSIONS: We describe the variability of the paediatric heart morphology and identify anatomical features related to childhood obesity that could aid in risk stratification. Web service is released to provide access to the new shape parameters.

Intensive Lifestyle Management Improves Steatosis and Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Childhood obesity, with associated comorbidities such as nonalcoholic fatty liver disease (NAFLD), is an increasing global health problem. Although lifestyle management is the mainstay of treatment, its efficacy on liver fibrosis has not yet been established. METHODS: Children and adolescents admitted for severe obesity at a tertiary center (Zeepreventorium, De Haan, Belgium) were enrolled in this prospective study. Intensive lifestyle therapy encompassed caloric restriction, physical activity, education on a healthy lifestyle, and psychosocial support. At baseline, 6 months, and 12 months, liver ultrasound and transient elastography with controlled attenuation parameter were performed to assess liver steatosis and fibrosis. RESULTS: A total of 204 patients (median age, 14.0 y; body mass index Z-score, +2.8) were evaluated at admission. NAFLD on ultrasound was present in 71.1%, whereas 68.6% had controlled attenuation parameter values of 248 dB/m or greater. A total of 32.8% of patients had at least F2 fibrosis, including 10.3% with transient elastography of 9 kPa or greater. After 6 months, the median body weight loss was 16.0% in the 167 patients evaluated. Fibrosis improved in 75.0% (P < .001). Baseline severity of liver fibrosis and steatosis were predictors of fibrosis resolution. Seventy-nine patients had reached the 1-year time point. The improvements were sustained because fibrosis regressed at least 1 stage in all patients with baseline fibrosis. Fasting serum alanine aminotransferase and homeostasis model assessment of insulin resistance decreased significantly over the 1-year period (P < .001). CONCLUSIONS: NAFLD and associated fibrosis are highly prevalent in children and adolescents with severe obesity. An intensive multidisciplinary lifestyle management program that causes significant weight loss not only improves liver steatosis, but also fibrosis.

Redox Imbalance and Methylation Disturbances in Early Childhood Obesity.

Obesity is increasing worldwide in prepubertal children, reducing the age of onset of associated comorbidities, including type 2 diabetes. Sulfur-containing amino acids, methionine, cysteine, and their derivatives play important roles in the transmethylation and transsulfuration pathways. Dysregulation of these pathways leads to alterations in the cellular methylation patterns and an imbalanced redox state. Therefore, we tested the hypothesis that one-carbon metabolism is already dysregulated in prepubertal children with obesity. Peripheral blood was collected from 64 children, and the plasma metabolites from transmethylation and transsulfuration pathways were quantified by HPLC. The cohort was stratified by BMI z-scores and HOMA-IR indices into healthy lean (HL), healthy obese (HO), and unhealthy obese (UHO). Fasting insulin levels were higher in the HO group compared to the HL, while the UHO had the highest. All groups presented normal fasting glycemia. Furthermore, high-density lipoprotein (HDL) was lower while triglycerides and lactate levels were higher in the UHO compared to HO subjects. S-adenosylhomocysteine (SAH) and total homocysteine levels were increased in the HO group compared to HL. Additionally, glutathione metabolism was also altered. Free cystine and oxidized glutathione (GSSG) were increased in the HO as compared to HL subjects. Importantly, the adipocyte secretory function was already compromised at this young age. Elevated circulating leptin and decreased adiponectin levels were observed in the UHO as compared to the HO subjects. Some of these alterations were concomitant with alterations in the DNA methylation patterns in the obese group, independent of the impaired insulin levels. In conclusion, our study informs on novel and important metabolic alterations in the transmethylation and the transsulfuration pathways in the early stages of obesity. Moreover, the altered secretory function of the adipocyte very early in life may be relevant in identifying early metabolic markers of disease that may inform on the increased risk for specific future comorbidities in this population.

Newer Insights Into Fetal Growth and Body Composition.

Based on epidemiological and experimental evidence, the origins of childhood obesity and early onset metabolic syndrome can be extended back to developmental processes during intrauterine life. It is necessary to actively investigate antecedent conditions that affect fetal growth by developing reliable measures to identify variations in fetal fat deposition and body composition. Recently, the resolution of ultrasonography has remarkably improved, which enables better tissue characterization and quantification of fetal fat accumulation. In addition, fetal fractional limb volume has been introduced as a novel measure to quantify fetal soft tissue volume, including fat mass and lean mass. Detecting extreme variations in fetal fat deposition may provide further insights into the origins of altered fetal body composition in pathophysiological conditions (i.e., fetal growth restriction or fetal macrosomia), which are predisposed to the metabolic syndrome in later life. Further studies are warranted to determine the maternal or placental factors that affect fetal fat deposition and body composition. Elucidating these factors may help develop clinical interventions for altered fetal growth and body composition, which could potentially lead to primary prevention of the future risk of metabolic dysfunction.

Evidence from a meta-analysis for association of MC4R rs17782313 and FTO rs9939609 polymorphisms with susceptibility to obesity in children.

BACKGROUND AND AIM: The aim of this study was to evaluate the association of MC4R rs17782313 and FTO rs9939609 polymorphisms with childhood obesity. METHODS: A universal search was performed up to May 2021. RESULTS: A total of 31 studies including 13 studies with 9565 cases and 11956 controls on MC4R rs17782313 and 18 studies with 4789 cases and 15918 controls on FTO rs9939609 were selected. CONCLUSIONS: Pooled data showed that FTO rs9930506 and MC4R rs17782313 polymorphisms were significantly associated with obesity in children. Stratified analyses revealed that these genetic variants were associated with childhood obesity in Caucasian and Asian children.

Association of muscle mass and fat mass on low-density-lipoprotein cholesterol and triglyceride plasma concentration in children and adolescents.

OBJECTIVES: Obesity has often been associated with high low-density-lipoprotein cholesterol (LDL-C) and triglyceride plasma concentrations, known risk factors for diabetes mellitus and cardiovascular disease. Study objective was to evaluate the association of LDL-C and triglyceride plasma concentration with muscle and fat mass in children and adolescents. METHODS: We analyzed data of the National Health and Nutrition Examination Survey (1999-2004) to estimate lean muscle and fat mass assessed by dual-energy X-ray absorptiometry (DXA) of participants whose lipid profiles had been examined. Fat mass was operationalized by DXA-determined fat mass index (FMI). Muscle mass was assessed by appendicular lean mass index (aLMI). High LDL-C and triglyceride concentration was defined as above 130 mg/dL. RESULTS: For the evaluation of the association of LDL-C and triglyceride plasma concentration with LMI and FMI Z-scores, the data of 2,487 children and adolescents (age 8-19 years) (984 females) were eligible. High aLMI showed no association with LDL-C or triglyceride concentration, but high FMI showed significant association with LDL-C and triglyceride plasma concentration in the bivariate regression analysis. CONCLUSIONS: Isolated muscle mass increase may not be protective against high LDL-C and triglycerides plasma levels in children and adolescents. Thus, exercise may lead to risk factor reduction mainly through fat mass reduction.

PNPLA3 Genotype, Arachidonic Acid Intake, and Unsaturated Fat Intake Influences Liver Fibrosis in Hispanic Youth with Obesity.

Non-alcoholic fatty liver disease impacts 15.2% of Hispanic adolescents and can progress to a build-up of scared tissue called liver fibrosis. If diagnosed early, liver fibrosis may be reversible, so it is necessary to understand risk factors. The aims of this study in 59 Hispanic adolescents with obesity were to: (1) identify potential biological predictors of liver fibrosis and dietary components that influence liver fibrosis, and (2) determine if the association between dietary components and liver fibrosis differs by PNPLA3 genotype, which is highly prevalent in Hispanic adolescents and associated with elevated liver fat. We examined liver fat and fibrosis, genotyped for PNPLA3 gene, and assessed diet via 24-h diet recalls. The prevalence of increased fibrosis was 20.9% greater in males, whereas participants with the GG genotype showed 23.7% greater prevalence. Arachidonic acid was associated with liver fibrosis after accounting for sex, genotype, and liver fat (ß = 0.072, p = 0.033). Intakes of several dietary types of unsaturated fat have different associations with liver fibrosis by PNPLA3 genotype after accounting for sex, caloric intake, and liver fat. These included monounsaturated fat (ßCC/CG = -0.0007, ßGG = 0.03, p-value = 0.004), polyunsaturated fat (ßCC/CG = -0.01, ßGG = 0.02, p-value = 0.01), and omega-6 (ßCC/CG = -0.0102, ßGG = 0.028, p-value = 0.01). Results from this study suggest that reduction of arachidonic acid and polyunsaturated fatty acid intake might be important for the prevention of non-alcoholic fatty liver disease progression, especially among those with PNPLA3 risk alleles.

Physiotherapy and related management for childhood obesity: A systematic scoping review.

INTRODUCTION: Despite targeted efforts globally to address childhood overweight/obesity, it remains poorly understood and challenging to manage. Physiotherapists have the potential to manage children with obesity as they are experts in movement and physical activity. However, their role remains unclear due to a lack of physiotherapy-specific guidelines. This scoping review aims to explore existing literature, critically appraising and synthesising findings to guide physiotherapists in the evidence-based management of childhood overweight/obesity. METHOD: A scoping review was conducted, including literature up to May 2020. A review protocol exists on Open Science Framework at https://osf.io/fap8g/. Four databases were accessed including PubMed, Embase, CINAHL, Medline via OVID, with grey literature searched through google via "file:pdf". A descriptive synthesis was undertaken to explore the impact of existing interventions and their efficacy. RESULTS: From the initial capture of 1871 articles, 263 intervention-based articles were included. Interventions included qualitative focused physical activity, quantitative focused physical activity and multicomponent interventions. Various outcome measures were utilised including health-, performance- and behaviour-related outcomes. The general trend for physiotherapy involvement with children who are obese appears to favour: 1) multicomponent interventions, implementing more than one component with environmental modification and parental involvement and 2) quantitative physical activity interventions, focusing on the quantity of bodily movement. These approaches most consistently demonstrated desirable changes across behavioural and health-related outcome measures for multicomponent and quantitative physical activity interventions respectively. CONCLUSION: When managing children with obesity, physiotherapists should consider multicomponent approaches and increasing the quantity of physical activity, given consistent improvements in various obesity-related outcomes. Such approaches are well suited to the scope of physiotherapists and their expertise in physical activity prescription for the management of childhood obesity. Future research should examine the effect of motor skill interventions and consider the role of environmental modification/parental involvement as factors contributing to intervention success.

Upregulated monocyte expression of PLIN2 is associated with early arterial injury in children with overweight/obesity.

BACKGROUND AND AIMS: Perilipin 2 (PLIN2) regulates intracellular lipid metabolism in macrophages, and thus, plays a role in atherosclerosis. Aim of the study was to evaluate whether PLIN2 dysregulation is involved in the onset of preclinical atherosclerosis in children with overweight/obesity and to explore dysregulation mechanisms. METHODS: Sixty-three children with overweight/obesity and 21 normal weight children (controls) of the same age and sex were enrolled. Carotid intima media thickness (cIMT) was evaluated; mRNA expression of PLIN2 and proteasome subunits (PSMD3, PSMC4) was determined by Real Time PCR, and protein expression of PLIN2, LAMP2A and Hsc70 by Western blot analysis; fluorimetric assay was used to measure proteasome chymotrypsin like activity. We performed transient LAMP2A downregulation by siRNA and quantified intracellular lipids in monocytes by Nile Red staining and flow cytometry analysis. RESULTS: PLIN2 protein levels were significantly higher in children with overweight/obesity and correlated with cIMT after adjusting for confounders. Accordingly, monocytes of children with overweight/obesity showed a higher intracellular amount of lipids compared with controls. mRNA expression of the regulatory subunits PSMC4 and PSMD3 and proteasome activity were lower in children with overweight/obesity, while expression of LAMP2A and Hsc70 proteins, which belong to the chaperone-mediated autophagy (CMA) pathway, was not different, suggesting that PLIN2 dysregulation in monocytes was due to an impairment of proteasome efficiency and was not CMA related. CONCLUSION: PLIN2 was overexpressed in monocytes of children with overweight/obesity and could contribute to the onset of arteropathy. Our data suggest that proteasome impairment could contribute to PLIN2 overexpression.

La falacia de los niños gordos anémicos / The fallacy of the fat anemic child

Fundamento: los estudios sugieren la presencia de deficiencia de hierro en niños obesos, lo que conduciría a una mayor incidencia de anemia en este grupo. Objetivo: evaluar la prevalencia de anemia entre niños con sobrepeso y obesidad de dos niveles socioeconómicos y dos regiones diferentes en Brasil. Métodos: se obtuvieron datos de hemoglobina y antropometría de 598 niños y adolescentes con sobrepeso y obesidad de dos servicios especializados en la atención de estos niños. Resultados: la prevalencia global de anemia fue del 5,8% y el nivel medio de hemoglobina fue de 13,2 mg / dL, sin diferencia estadística para los dos indicadores según sobrepeso u obesidad y grupo de edad. Sin embargo, la hemoglobina media fue mayor entre los varones y, en el servicio con atención prestada a una población de menor nivel socioeconómico, la prevalencia de anemia fue mayor. Conclusión: la prevalencia de anemia encontrada en niños y adolescentes con sobrepeso y obesidad fue bastante baja, siendo mayor en la población más pobre. Para los niños y adolescentes con sobrepeso, la anemia parece estar más relacionada con el nivel socioeconómico que con la presencia de exceso de peso.

Background: studies suggest the presence of iron deficiency among obese children, which would lead to a higher incidence of anemia in this group. Aim: to assess the prevalence of anemia among overweight and obese children from two socioeconomic levels and two different regions in Brazil. Methods: hemoglobin and anthropometric data on 598 overweight and obese children and adolescents were obtained from two services specialized in the care of these children. Results: the overall prevalence of anemia was 5.8% and mean hemoglobin level was 13.2 mg/dL, with no statistical difference for the two indicators according to overweight or obesity and age group. However, the mean hemoglobin was higher among boys and, in the service with care provided to a population of lower socioeconomic status, the prevalence of anemia was higher. Conclusion: the prevalence of anemia found among overweight and obese children and adolescents was quite low, being higher in the poorest population. For overweight children and adolescents, anemia seems to be more related to socioeconomic status than to the presence of excess weight.

A prediction model for childhood obesity in New Zealand.

Several early childhood obesity prediction models have been developed, but none for New Zealand's diverse population. We aimed to develop and validate a model for predicting obesity in 4-5-year-old New Zealand children, using parental and infant data from the Growing Up in New Zealand (GUiNZ) cohort. Obesity was defined as body mass index (BMI) for age and sex ≥ 95th percentile. Data on GUiNZ children were used for derivation (n = 1731) and internal validation (n = 713). External validation was performed using data from the Prevention of Overweight in Infancy Study (POI, n = 383) and Pacific Islands Families Study (PIF, n = 135) cohorts. The final model included: birth weight, maternal smoking during pregnancy, maternal pre-pregnancy BMI, paternal BMI, and infant weight gain. Discrimination accuracy was adequate [AUROC = 0.74 (0.71-0.77)], remained so when validated internally [AUROC = 0.73 (0.68-0.78)] and externally on PIF [AUROC = 0.74 [0.66-0.82)] and POI [AUROC = 0.80 (0.71-0.90)]. Positive predictive values were variable but low across the risk threshold range (GUiNZ derivation 19-54%; GUiNZ validation 19-48%; and POI 8-24%), although more consistent in the PIF cohort (52-61%), all indicating high rates of false positives. Although this early childhood obesity prediction model could inform early obesity prevention, high rates of false positives might create unwarranted anxiety for families.