Insights from shotgun metagenomics into bacterial species and metabolic pathways associated with NAFLD in obese youth

Background and Aims NAFLD is the most common form of liver disease and is often the precursor for more serious liver conditions such as NASH and cirrhosis. The gut microbiome has been implicated in the development of NAFLD, but studies have often compared healthy individuals to those with the disease. In this study, we aimed to examine the taxonomic and functional differences between the microbiomes of obese youth with and without NAFLD. Approach and Results Shotgun metagenome sequencing was used to profile the microbial communities of 36 subjects, half of which were diagnosed with NAFLD. Beta diversity analysis showed community-wide differences between the cohorts (p = 0.002). Specific taxonomic differences included the species Fusicatenibacter saccharivorans (p = 0.042), Romboutsia ilealis (p = 0.046), and Actinomyces sp. ICM47 (p = 0.0009) elevated in the NAFLD-positive group and Bacteroides thetaiotamicron (p = 0.0002) elevated in the NAFLD-negative group. At the phylum level, Bacteroidetes (p < 0.0001) was elevated in the NAFLD-negative group. Functionally, branched chain amino acid (p = 0.01343) and aromatic amino acid (p = 0.01343) synthesis pathways were elevated in the NAFLD-positive group along with numerous energy utilization pathways including pyruvate fermentation to acetate (p = 0.01318). Conclusions The link between obesity and NAFLD development in younger individuals has rarely been probed, with most studies focusing on adults and comparing healthy individuals with obese, NAFLD-positive individuals. This study supports the idea that the NAFLD phenotype displays a differentiated microbial and functional signature from the obesity phenotype.

Quantifying parent engagement in the randomized Fuel for Fun impact study identified design considerations and BMI relationships

Background Parent participation in children’s health interventions is insufficiently defined and measured. This project quantified parent participation to enable future examination with outcomes in an intervention focused on 4th graders, aged 9–11 years, and their families living in northern Colorado. Methods Indices were developed to measure type (Parent Participation Profile; PPP) and intensity (Parent Engagement Intensity; PEI) of engagement in Fuel for Fun (FFF), an asymmetric school-and family-based intervention for 4th graders. Study arm-specific participation opportunities were catalogued and summed to calculate the PPP. An algorithm considered frequency, effort, convenience, and invasiveness of each activity to calculate PEI. Indices were standardized (0–100%) using study arm-specific divisors to address asymmetric engagement opportunities. Parents who completed ≥75% of the PPP were defined as Positive Deviants. Youth height and weight were measured. Youth BMI percentile change was compared with parent Positive Deviant status using general linear modeling with repeated measures that included the participation indices. Results Of 1435 youth, 777 (54%) had parent participation in at least one activity. Standardized means were 41.5 ± 25.4% for PPP and 27.6 ± 20.9% for PEI. Demographics, behaviors or baseline FFF outcomes did not differ between the Positive Deviant parent (n = 105) and non-Positive Deviant parents (n = 672); but more Positive Deviant parents followed an indulgent feeding style (p = 0.015). Standardized intensity was greater for Positive Deviant parents; 66.9 ± 20.6% vs 21.5 ± 12.7% (p < 0.001) and differences with non-Positive Deviant parents were related to activity type (p ≤0.01 for six of eight activities). Standardized participation intensity was associated with engagement in a greater number of standardized activity types. Among participating parents, standardized intensity and breadth of activity were inversely related to the youth BMI percentile (n = 739; PEI r = −0.39, p < 0.001; PPP r = −0.34, p < 0.001). Parent engagement was not associated with parent BMI change. Conclusions An activity-specific intensity schema operationalized measurement of parent engagement in a complex, unbalanced research design and can serve as a template for more sensitive assessment of parent engagement. Positive deviance in parent engagement was not a function of personal, but rather activity characteristics. PPP and PEI increased with fewer requirements and convenient, novel, and personalized activities. Parent engagement indices affirmed lower engagement by parents of overweight/obese youth and concerns about target reach.

Relationship Between Nonalcoholic Fatty Liver Disease and Low Skeletal Muscle Mass in Obese Youth

Previous studies in adults have found a correlation between nonalcoholic fatty liver disease (NAFLD) and sarcopenia. The present study evaluated the relationship between NFALD and skeletal muscle mass in overweight/obese youth. A total of 234 children and adolescents (age 8-16) was stratified into tertiles based on relative muscle mass (RMM). Total, regional lean body mass, and total fat mass were obtained by dual-energy X-ray absorptiometry. RMM was defined as the percent of muscle mass (kg) relative to the sum of muscle and fat mass (kg). NAFLD was diagnosed via ultrasononography and a subset of participants with NAFLD (n=40) underwent a liver biopsy. The lowest tertile had a significantly higher risk for obesity, dyslipidemia, insulin resistance, metabolic syndrome, NAFLD, and nonalcoholic steatohepatitis (NASH). The present study demonstrated an association between low muscle mass, NAFLD, and NASH in overweight/obese youth. Despite the strong scientific merits of the present study, a lack of race/ethnic description could be a major critique as different ethnic background (specifically in the minorities) may be disproportionately impacted by fat distribution and relative muscle mass. Even though there is a clear relationship between sarcopenia and NAFLD in the elderly, this association may not stem from the same origin in the pediatric population. Lastly, but not least, future studies should evaluate NAFLD in obese youth with varying degrees of metabolic disorders (i.e., metabolic syndrome).

Low Muscular Strength, Weight Status, and Metabolic Syndrome in Adolescents: National Health and Nutrition Examination Survey 2011–2014

Purpose: To investigate the association between muscular strength and metabolic syndrome (MetS), with a specific focus on the role of weight status, using a nationally representative sample of US youth. Methods: The analysis included 409 boys and 415 girls from the 2011 to 2014 National Health and Nutrition Examination Survey between 12 and 18 years of age. The prevalence of MetS was defined using age- and sex-specific criteria for abdominal obesity, elevated triglycerides, blood pressure, fasting glucose, and low high-density lipoprotein (HDL) cholesterol. Strength was assessed via handgrip dynamometer and expressed as age- and sex-specific z scores of relative strength. Low strength was defined as a relative strength below the 25th percentile. Analyses controlled for age, sex, race/ethnicity, physical activity, and weight status. Results: The sample prevalence of MetS was approximately 5.3%. However, MetS prevalence was 18.5% in overweight/obese youth with low strength. The adjusted odds of MetS were 3.1 (95% confidence interval, 1.5–6.3, P < .001) times higher for overweight/obese youth with low strength versus sufficient strength. Conclusion: Muscular strength is predictive of adolescent MetS, specifically in those with unhealthy weight status. Approximately one in 5 overweight/obese youth with low strength had MetS. These findings highlight the relevance of muscular strength in youth cardiometabolic morbidities.

Altered adipokines in obese adolescents: A cross-sectional and longitudinal analysis across the spectrum of glycemia

Obesity and type 2 diabetes is rapidly increasing in the adolescent population. We sought to determine whether adipokines, specifically leptin, C1q/TNF-related proteins 1 (CTRP1) and CTRP9, and the hepatokine fibroblast growth factor 21 (FGF-21), are associated with obesity and insulin resistance in a cohort of lean and obese adolescents, across the spectrum of glycemia. In an observational, longitudinal study of lean and obese adolescents, we measured fasting labs, oral glucose tolerance tests, and adipokines including: Leptin, CTRP1, CTRP9, and FGF-21. Participants completed baseline and 2-year follow-up study visits, and were categorized as lean (n=30), obese normoglycemic (ONG) (n=61), and obese hyperglycemic (OHG) (n=31) adolescents at baseline, and lean (n=8), ONG (n=18), and OHG (n=4) at follow-up. Results showed that at baseline, leptin was higher in all obese groups (p<0.001) compared to LC. FGF-21 was higher in OHG participants compared to LC (p<0.001) and ONG (p<0.001), and positively associated with fasting glucose (p<0.001), fasting insulin (p<0.001), HOMA-IR (p<0.001), and HbA1c (p=0.01). CTRP1 was higher in OHG compared to ONG (p=0.03). CTRP9 was not associated with obesity or hyperglycemia in this pediatric cohort. At 2 years, leptin decreased in ONG (p=0.003) and FGF21 increased in OHG (p=0.02), relative to lean controls. Altered adipokine levels are associated with the inflammatory milieu in obese youth with and without hyperglycemia. In adolescence, the novel adipokine CTRP1 was elevated with hyperglycemia, while CTRP9 was unchanged in this cohort.