Balagopal, P Babu

Abstract Background Prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction‐associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N ‐acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) in children with obesity and biopsy‐confirmed MASLD. Methods Thirteen children ( n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double‐blind, placebo‐controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high‐sensitivity c‐reactive protein (hs‐CRP), and interleukin‐6 (IL‐6) were also measured. homeostasis model assessment for insulin resistance (HOMA‐IR) was calculated. Results Sixteen‐week NAC treatment improved (baseline adjusted between‐group p < .05 for all) markers of inflammation (IL‐6 and hs‐CRP), oxidative stress (GSH), and IR (HOMA‐IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes. Conclusions Sixteen‐week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD.

Abstract Context Elevated concentrations of branched-chain amino acids (BCAA) are strong predictors of type 2 diabetes mellitus (T2DM). Their association with cardiovascular disease (CVD) remains uncertain, particularly in youth. Objective We investigated the role of BCAA and aromatic amino acids (AAA) in obesity, their relationships with novel biomarkers of CVD, and response to a physical activity-based lifestyle intervention (PAL-I) in a randomized controlled study in youth with normal weight (NW) and obesity (OB). Methods Age (14-18 years) and Tanner stage (≥IV) matched youth (OB, n = 15 and NW, n = 6) were studied; the 15 participants with OB underwent a 3-month randomized controlled PAL-I. Circulating amino acid profile, glucose, insulin, lipids, adiponectin, retinol binding protein-4, fibrinogen, high-sensitivity C-reactive protein, interleukin-6, and 25-hydroxy vitamin-D, along with body composition, were measured at baseline and after PAL-I. Independent t tests, analysis of covariance, and mixed-effect models were used for analysis of the data. Results Compared with NW, the concentration of various amino acids, including BCAA and AAA, were altered in OB (P &lt; 0.05). BCAA and AAA showed baseline correlations with body composition and novel biomarkers of CVD, particularly inflammatory factors (all P &lt; 0.05). The PAL-I produced only negligible effects (P &gt; 0.05) on BCAA and AAA. Glutamine, glycine, and aspartic acid decreased with PAL-I (all P &lt; 0.05). Conclusion The novel finding of the BCAA–inflammation relationship, along with strong correlations with nontraditional biomarkers of CVD, may raise the prospect of BCAA as a biomarker of CVD and evoke a potential link between obesity, T2DM, and CVD.

AbstractBackground and AimThis study aimed to evaluate the impact of physical activity (PA) on the course of hepatic steatosis (HS) in adults.MethodsHepatic steatosis status (ultrasonography) and PA levels were evaluated in 5860 subjects at baseline and after approximately 2.5 years (range: 19–50 months). At follow up, possible exposures to different PA levels were those who remained inactive, became inactive, became active, and remained active. After follow up, subjects were then classified according to the four possible states (outcomes): “remained without HS,” “developed HS” (subjects without HS at baseline), “remained with HS,” or “reverted HS.”ResultsAfter multivariate adjustments, individuals without HS that became or remained physically active were less likely to develop HS compared with those who remained physically inactive (odds ratio = 0.75, P = 0.04 and 0.75, P = 0.03, respectively). Among those with HS at baseline, becoming and remaining physically active beneficially improved the HS status (odds ratio = 0.64, P = 0.01 and 0.66, P = 0.01, respectively). However, the significance was lost when adjusted for changes in body mass index.ConclusionHigher levels of PA were associated with prevention and treatment of HS, with evidence of effect mediation by changes in body mass index.