Open Access
Development of a prediction protocol for the screening of metabolic associated fatty liver disease in children with overweight or obesity
(Wiley, 2022) Osés Recalde, Maddi; Cadenas-Sánchez, Cristina; Medrano Echeverría, María; Galbete Jiménez, Arkaitz; Miranda Ferrúa, Emiliano; Ruiz, Jonatan R.; Sánchez-Valverde, Félix; Ortega, Francisco B.; Cabeza Laguna, Rafael; Villanueva Larre, Arantxa; Idoate, Fernando; Labayen Goñi, Idoia; Osasun Zientziak; Institute of Smart Cities - ISC; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Ciencias de la Salud; Gobierno de Navarra / Nafarroako Gobernua
Background: the early detection and management of children with metabolic associ-ated fatty liver disease (MAFLD) is challenging. Objective: to develop a non-invasive and accurate prediction protocol for the identi-fication of MAFLD among children with overweight/obesity candidates to confirma-tory diagnosis. Methods: a total of 115 children aged 8–12 years with overweight/obesity, rec-ruited at a primary care, were enrolled in this cross-sectional study. The external vali-dation was performed using a cohort of children with overweight/obesity (N=46)aged 8.5–14.0 years. MAFLD (≥5.5% hepatic fat) was diagnosed by magnetic reso-nance imaging (MRI). Fasting blood biochemical parameters were measured, and25 candidates’ single nucleotide polymorphisms (SNPs) were determined. Variablespotentially associated with the presence of MAFLD were included in a multivariatelogistic regression. Results: children with MAFLD (36%) showed higher plasma triglycerides (TG),insulin, homeostasis model assessment ofinsulin resistance (HOMA-IR), alanineaminotransferase (ALT), aspartate transaminase (AST), glutamyl-transferase (GGT)and ferritin (p< 0.05). The distribution of the risk-alleles of PPARGrs13081389, PPARGrs1801282, HFErs1800562 and PNLPLA3rs4823173 was significantly different between children with and without MAFLD (p<0.05). Threebiochemical- and/or SNPs-based predictive models were developed, showingstrong discriminatory capacity (AUC-ROC: 0.708–0.888) but limited diagnosticperformance (sensitivity 67%–82% and specificity 63%–69%). A prediction proto-col with elevated sensitivity (72%) and specificity (84%) based on two consecutive steps was developed. The external validation showed similar results: sensitivity of 70% and specificity of 85%. Conclusions: the HEPAKID prediction protocol is an accurate, easy to implant, minimally invasive and low economic cost tool useful for the early identification and management of paediatric MAFLD in primary care.
Open Access
Effects of exercise on bone marrow adipose tissue in children with overweight/obesity: role of liver fat
(Oxford University Press, 2024-08-07) Labayen Goñi, Idoia; Cadenas-Sánchez, Cristina; Idoate, Fernando; Gracia-Marco, Luis; Medrano Echeverría, María; Alfaro-Magallanes, Víctor Manuel; Alcántara Alcántara, Juan Manuel; Rodríguez Vigil, Beatriz; Osés Recalde, Maddi; Ortega, Francisco B.; Ruiz, Jonatan R.; Cabeza Laguna, Rafael; Ingeniería Eléctrica, Electrónica y de Comunicación; Ingeniaritza Elektrikoa, Elektronikoa eta Telekomunikazio Ingeniaritza; Agronomía, Biotecnología y Alimentación; Agronomia, Bioteknologia eta Elikadura; Ciencias de la Salud; Osasun Zientziak; Institute of Smart Cities - ISC; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Gobierno de Navarra / Nafarroako Gobernua
Context: Exercise reduces adiposity, but its influence on bone marrow fat fraction (BMFF) is unknown; nor is it known whether a reduction in liver fat content mediates this reduction. Objectives: This work aimed to determine whether incorporating exercise into a lifestyle program reduces the lumbar spine (LS) BMFF and to investigate whether changes in liver fat mediate any such effect.Methods Ancillary analysis of a 2-arm, parallel, nonrandomized clinical trial was conducted at primary care centers in Vitoria-Gasteiz, Spain. A total of 116 children with overweight/obesity were assigned to a 22-week family-based lifestyle program (control group [n = 57]) or the same program plus an exercise intervention (exercise group [n = 59]). The compared interventions consisted of a family-based lifestyle program (two 90-minute sessions/month) and the same program plus supervised exercise (three 90-minute sessions/week). The primary outcome examined was the change in LS-BMFF between baseline and 22 weeks, as estimated by magnetic resonance imaging. The effect of changes in hepatic fat on LS-BMFF were also recorded.Results Mean weight loss difference between groups was 1.4 +/- 0.5 kg in favor of the exercise group. Only the children in the exercise group experienced a reduction in LS-BMFF (effect size [Cohen d] -0.42; CI, -0.86 to -0.01). Importantly, 40.9% of the reductions in LS-BMFF were mediated by changes in percentage hepatic fat (indirect effect: beta=-0.104; 95% CI, -0.213 to -0.019). The effect of changes in hepatic fat on LS-BMFF was independent of weight loss.Conclusion The addition of exercise to a family-based lifestyle program designed to reduce cardiometabolic risk improves bone health by reducing LS-BMFF in children with overweight or obesity. This beneficial effect on bone marrow appears to be mediated by reductions in liver fat.
Open Access
Peripheral blood mononuclear cells-expressed miRNA profiles derived from children with metabolic-associated fatty liver disease and insulin resistance
(Wiley, 2022) Osés Recalde, Maddi; Medrano Echeverría, María; Margareto, Javier; Portillo, María P.; Aguilera, Concepción María; Altmäe, Signe; Labayen Goñi, Idoia; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Gobierno de Navarra / Nafarroako Gobernua
Background: miRNA have been proposed as potential biomarkers of metabolic diseases. Objectives: To identify potential miRNA biomarkers of early metabolic-associated fatty liver disease (MAFLD) and/or insulin resistance (IR) in preadolescent children. Methods: A total of 70 preadolescents, aged 8.5–12 years old participated in the study. Hepatic fat was assessed by magnetic resonance imaging. Fasting blood biochemical parameters were measured and HOMA-IR calculated. Peripheral blood mononuclear cells (PBMC)-derived miRNA profiles associated with MAFLD (≥5.5% hepatic fat) and IR (HOMA-IR ≥2.5) were identified using untargeted high-throughput miRNAs sequencing (RNA-seq). Results: A total of 2123 PBMC-derived miRNAs were identified in children with (21.4%) or without MAFLD. Among them, hsa-miR-143-3p, hsa-miR-142-5p and hsamiR-660-5p were up-regulated, and p-hsa-miR-247, hsa-let-7a-5p and hsa-miR6823-3p down-regulated. Importantly, children with MAFLD had consistently higher miR-660-5p expression levels than their peers without it (p < 0.01), regardless of weight status. A total of 2124 PBMC-derived miRNA were identified in children with IR (28.6%) versus children without IR, where thirteen of them were dysregulated (p < 0.05) in children with IR. In addition, children with IR showed higher levels of miR-374a-5p and miR-190a-5p (p < 0.01) and lower levels of miR-4284 and miR4791 (p < 005), than their peers without IR in both the whole sample and in those with overweight or obesity. Conclusions: Our study results suggest circulating miR-660-5p as a potential biomarker of the presence of MAFLD in preadolescent children while circulating miR320a, miR-142-3p, miR-190a-5p, miR-374a-5p and let-7 family miRNAs could serve as potential biomarkers of IR in children.

Medrano Echeverría, María

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