Open Access
The effect of a multicomponent intervention on steatosis is partially mediated by the reduction of intermuscular abdominal adipose tissue in children with overweight or obesity: the EFIGRO Project
(American Diabetes Association, 2022) Cadenas-Sánchez, Cristina; Idoate, Fernando; Cabeza Laguna, Rafael; Villanueva Larre, Arantxa; Rodríguez Vigil, Beatriz; Medrano Echeverría, María; Osés Recalde, Maddi; Ortega, Francisco B.; Ruiz, Jonatan R.; Labayen Goñi, Idoia; Osasun Zientziak; Ingeniaritza Elektrikoa, Elektronikoaren eta Telekomunikazio Ingeniaritzaren; Institute of Smart Cities - ISC; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Ciencias de la Salud; Ingeniería Eléctrica, Electrónica y de Comunicación; Gobierno de Navarra / Nafarroako Gobernua
OBJECTIVE: In adults, there is evidence that improvement of metabolic-associated fatty liver disease (MAFLD) depends on the reduction of myosteatosis. In children, in whom the prevalence of MAFLD is alarming, this muscle-liver crosstalk has not been tested. Therefore, we aimed to explore whether the effects of a multicomponent intervention on hepatic fat is mediated by changes in intermuscular abdominal adipose tissue (IMAAT) in children with overweight/obesity. RESEARCH DESIGN AND METHODS: A total of 116 children with overweight/obesity were allocated to a 22-week family-based lifestyle and psychoeducational intervention (control group, n = 57) or the same intervention plus supervised exercise (exercise group, n = 59). Hepatic fat percentage and IMAAT were acquired by MRI at baseline and at the end of the intervention. RESULTS: Changes in IMAAT explained 20.7% of the improvements in hepatic steatosis (P < 0.05). Only children who meaningfully reduced their IMAAT (i.e., responders) had improved hepatic steatosis at the end of the intervention (within-group analysis: responders -20% [P = 0.005] vs. nonresponders -1.5% [P = 0.803]). Between-group analysis showed greater reductions in favor of IMAAT responders compared with nonresponders (18.3% vs. 0.6%, P = 0.018), regardless of overall abdominal fat loss. CONCLUSIONS: The reduction of IMAAT plays a relevant role in the improvement of hepatic steatosis after a multicomponent intervention in children with overweight/obesity. Indeed, only children who achieved a meaningful reduction in IMAAT at the end of the intervention had a reduced percentage of hepatic fat independent of abdominal fat loss. Our findings suggest that abdominal muscle fat infiltration could be a therapeutic target for the treatment of MAFLD in childhood.
Open Access
Differences in specific abdominal fat depots between metabolically healthy and unhealthy children with overweight/obesity: the role of cardiorespiratory fitness
(Wiley, 2023) Cadenas-Sánchez, Cristina; Medrano Echeverría, María; Villanueva Larre, Arantxa; Cabeza Laguna, Rafael; Idoate, Fernando; Osés Recalde, Maddi; Rodríguez Vigil, Beatriz; Álvarez de Eulate, Natalia; Alberdi Aldasoro, Nerea; Ortega, Francisco B.; Labayen Goñi, Idoia; Ciencias de la Salud; Ingeniería Eléctrica, Electrónica y de Comunicación; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Institute of Smart Cities - ISC; Osasun Zientziak; Ingeniaritza Elektrikoa, Elektronikoaren eta Telekomunikazio Ingeniaritzaren
Objectives: Fat depots localization has a critical role in the metabolic health status of adults. Nevertheless, whether that is also the case in children remains under- studied. Therefore, the aims of this study were: (i) to examine the differ-ences between metabolically healthy (MHO) and unhealthy (MUO) overweight/obesity phenotypes on specific abdominal fat depots, and (ii) to further explore whether cardiorespiratory fitness plays a major role in the differences between metabolic phenotypes among children with overweight/obesity. Methods: A total of 114 children with overweight/obesity (10.6 ±1.1 years, 62 girls) were included. Children were classified as MHO (n=68) or MUO. visceral (VAT), abdominal subcutaneous (ASAT), intermuscular abdominal (IMAAT), psoas, hepatic, pancreatic, and lumbar bone marrow adipose tissues were measured by magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20 m shuttle run test. Results: MHO children had lower VAT and ASAT contents and psoas fat fraction compared to MUO children (difference =12.4%– 25.8%, all p<0.035). MUO- unfit had more VAT and ASAT content than those MUO- fit and MHO- fit (difference =34.8%– 45.3%, all p<0.044). MUO- unfit shows also greater IMAAT fat fraction than those MUO- fit and MHO- fit peers (difference =16.4%– 13.9% respectively, all p≤0.001). In addition, MHO- unfit presented higher IMAAT fat fraction than MHO- fit (difference =13.4%, p<0.001). MUO- unfit presented higher psoas fat fraction than MHO- fit (difference =29.1%, p=0.008). Conclusions: VAT together with ASAT and psoas fat fraction, were lower in MHO than in MUO children. Further, we also observed that being fit, regardless of metabolic phenotype, has a protective role over the specific abdominal fat depots among children with overweight/obesity.
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
Effects of a family-based lifestyle intervention plus supervised exercise training on abdominal fat depots in children with overweight or obesity: a secondary analysis of a nonrandomized clinical trial
(American Medical Association, 2022) Cadenas-Sánchez, Cristina; Cabeza Laguna, Rafael; Idoate, Fernando; Osés Recalde, Maddi; Medrano Echeverría, María; Villanueva Larre, Arantxa; Arenaza Etxeberría, Lide; Sanz Muñoz, Aritz; Ortega, Francisco B.; Ruiz, Jonatan R.; Labayen Goñi, Idoia; Ciencias de la Salud; Ingeniería Eléctrica, Electrónica y de Comunicación; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Institute of Smart Cities - ISC; Osasun Zientziak; Ingeniaritza Elektrikoa, Elektronikoaren eta Telekomunikazio Ingeniaritzaren
Importance Excess abdominal fat is a major determinant in the development of insulin resistance and other metabolic disorders. Increased visceral adipose tissue (VAT) seems to precede the development of insulin resistance and is therefore a prime target of childhood lifestyle interventions aimed at preventing diabetes. OBJECTIVES To examine the effect of added exercise to a family-based lifestyle intervention program designed to reduce VAT plus subcutaneous (ASAT), intermuscular (IMAAT), and pancreatic (PAT) adipose tissue in children with overweight or obesity and to explore the effect of changes in VAT on insulin resistance. DESIGN, SETTING, AND PARTICIPANTS This 2-group, parallel-design clinical trial was conducted in Vitoria-Gasteiz, Spain. A total of 116 children with overweight or obesity participated and 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]). Data were collected between September 1, 2014, and June 30, 2017, and imaging processing for fat depot assessments and data analysis were performed between May 1, 2019, and February 12, 2021. INTERVENTIONS The compared interventions consisted of a family-based lifestyle and psychoeducation program (two 90-minute sessions per month) and the same program plus supervised exercise (three 90-minute sessions per week). MAIN OUTCOMES AND MEASURES The primary outcome of this study was the change in VAT between baseline and 22 weeks as estimated by magnetic resonance imaging. The secondary outcomes were changes in ASAT, IMAAT, and PAT. The effect of changes in VAT area on insulin resistance was also recorded. RESULTS The 116 participants included in the analysis (62 girls [53.4%]) had a mean (SD) age of 10.6 (1.1) years, and 67 (57.8%) presented with obesity. Significantly greater reductions were recorded for the exercise group in terms of reduction in VAT (−18.1% vs −8.5% for the control group; P = .004), ASAT (−9.9% vs −3.0%; P = .001), and IMAAT (−6.0% vs −2.6%; P = .02) fat fractions compared with the control group. Changes in VAT explained 87.6% of the improvement seen in insulin resistance (β = −0.102 [95% CI, −0.230 to −0.002]). CONCLUSIONS AND RELEVANCE These findings suggest that the addition of exercise to a lifestyle intervention program substantially enhanced the positive effects on abdominal fat depots in children with overweight or obesity. In addition, the reduction in VAT seemed to largely mediate the improvement of insulin sensitivity. These results highlight the importance of including exercise as part of lifestyle therapies aimed at treating childhood obesity and preventing the development of type 2 diabetes.
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.