4. Discussion
obesity, MASLD (hepatic steatosis, fibrosis, hepatic and muscle glucose, hepatic abnormalities, hepatic damage, steatosis
OBESITY, FIBROSIS, PATHOPHYSIOLOGY, REMISSION, HEPATIC STEATOSIS, HEPATIC DAMAGE, REGRESSION, HEPATIC FIBROSIS, STEATOSIS
In the present study, we described the metabolomic phenotypes associated with two stages of MASLD progression (MASLD (hepatic steatosis) and MASLD + fibrosis (hepatic steatosis + fibrosis)) in Mexican children with obesity compared to those with obesity but without MASLD. According to logistic regression models, MASLD was associated with a phenotype characterized by increased concentrations of ALT and decreased arginine, glycine, and AC5:1 (tiglylcarnitine). On the other hand, MASLD + fibrosis, a progression stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. This metabolic signature also identified MASLD + fibrosis children from the MASLD group. A major metabolic change in children affected with MAFLD + fibrosis results in the increased availability of amino acids in circulation.The VIP analyses identified other metabolite differences between groups; however, we wanted to select a reduced set of metabolites and biochemical data capable of identifying MASLD and MASLD + fibrosis groups that might be useful in clinical practice.ALT is a marker of hepatic damage and is widely used to screen MASLD, SH, and hepatic fibrosis in adults and children [Although ALT elevation is part of MASLD and MASLD + fibrosis phenotypes, other metabolites acted as metabolic signatures in each group. The MASLD phenotype included decreased concentrations of arginine, glycine, and AC5:1. The ROC area of this model was below 0.70, and the VIP scores were lower than 2.0; therefore, the measurement of these metabolites was not enough to identify the MASLD phenotype. Despite the above, other studies have found alterations in some of these metabolites. Arginine is essential in the urea cycle and is a precursor of nitric oxide (NO) [The MASLD + fibrosis phenotype included, in addition to increased ALT, increased proline and alanine and a decreased Matsuda Index. Proline is essential in the structure and function of proteins and is a major component of collagen [Increased ALT, proline, and alanine and a decreased Matsuda Index were characteristics of children with MASLD + fibrosis, which discriminated this group from the non-MASLD and MASLD subjects, indicating that these variables reflect specific changes that could be a consequence of the progression of MASLD to fibrosis. Consistent with our findings, a study conducted in a population of Mexican adults with obesity [From a practical and clinical point of view, it seems imperative to generate diagnostic tools in order to detect hepatic abnormalities in children with obesity in a timely manner, since the few available long-term studies have shown that the remission of SH in children and adolescents who participated in an intervention program was 30% in the case in which they did not receive any supplementation or medication; in contrast, with supplementation, remission was 58% and, with medication, it was 41% [Some limitations must be considered in the present study. First, the sample size was small. However, it was sufficient for identifying metabolic phenotypes that are consistent with the findings of other studies and the pathophysiology of MASLD, even though these metabolites are not yet routinely used. On the other hand, a liver biopsy was not performed, which we know is the gold standard for diagnosing steatosis and hepatic fibrosis; nonetheless, FibroScanA strength of this study is that all patients belonged to Class 1 obesity (which provides internal validity), they had similar genetic–environmental backgrounds, and they presented similar durations with respect to obesity. Moreover, we evaluated glucose metabolism using the Matsuda index, which more accurately reflects hepatic and muscle glucose sensitivity compared to those that consider a single blood determination. Additionally, to our knowledge, this is the first study aimed at identifying a metabotype for MASLD stages in Mexican children living with obesity.