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Letter to the Editor| Volume 75, ISSUE 6, P1511-1513, December 2021

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Intermuscular abdominal fat fraction and metabolic dysfunction-associated fatty liver disease: Does the link already exist in childhood?

  • Cristina Cadenas-Sanchez
    Correspondence
    Corresponding author. Address: Department of Health Sciences, Public University of Navarra, Calle Tajonar 22, Jerónimo de Ayanz Research building, 31006, Pamplona, Spain. Tel.: +34 948169796.
    Affiliations
    Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Public University of Navarra, Pamplona, Spain

    Department of Health Sciences, Public University of Navarra, Pamplona, Spain

    IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
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  • Fernando Idoate
    Affiliations
    Department of Health Sciences, Public University of Navarra, Pamplona, Spain

    Radiology Department, Mutua Navarra, Pamplona, Spain
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  • Arantxa Villanueva
    Affiliations
    IdiSNA, Navarra Institute for Health Research, Pamplona, Spain

    Smart Cities Institute, Public University of Navarra, Pamplona, Spain

    Department of Electrical, Electronic and Communications Engineering, Public University of Navarra, Pamplona, Spain
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  • Rafael Cabeza
    Affiliations
    Department of Electrical, Electronic and Communications Engineering, Public University of Navarra, Pamplona, Spain
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  • Idoia Labayen
    Affiliations
    Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Public University of Navarra, Pamplona, Spain

    Department of Health Sciences, Public University of Navarra, Pamplona, Spain

    IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
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      Linked Article

      To the Editor:
      We have read with great interest the study by Nachit et al.,
      • Nachit M.
      • Kwanten W.J.
      • Thissen J.-P.
      • Op de Beeck B.
      • Van Gaal L.
      • Vonghia L.
      • et al.
      Muscle fat content is strongly associated with NASH: a longitudinal study in patients with morbid obesity.
      wherein they show the contribution of muscle fat infiltration on the physiopathology of metabolic dysfunction-associated fatty liver disease (MAFLD) in adults with morbid obesity. We extend these findings by showing the association between intermuscular abdominal fat fraction (IMAAT) and MAFLD in children who are overweight/obese. Further, we report IMAAT differences by sex and weight status.
      We used baseline data on 116 children (10.6 ± 1.1 years, 62 girls) who were overweight or obese from the EFIGRO project (NCT02258126).
      • Labayen I.
      • Medrano M.
      • Arenaza L.
      • Maíz E.
      • Osés M.
      • Martínez-Vizcaíno V.
      • et al.
      Effects of exercise in addition to a family-based lifestyle intervention program on hepatic fat in children with overweight.
      Magnetic resonance imaging (Magnetom Avanto, 3T, Siemens) was used to assess the percentage hepatic fat and IMAAT at 3 axial slices (L2-L3, L3, and L4-L5), being the average used for analyses. Images were screened, delineated, and classified by experienced radiologists and researchers, and MAFLD was defined as having >5.0% hepatic fat. We used Gardner-Altman plots
      • Ho J.
      • Tumkaya T.
      • Aryal S.
      • Choi H.
      • Claridge-Chang A.
      Moving beyond P values: data analysis with estimation graphics.
      ,
      • Gardner M.J.
      • Altman D.G.
      Confidence intervals rather than P values: estimation rather than hypothesis testing.
      to compare IMAAT levels between children with and without MAFLD, as well as across the MAFLD spectrum, by sex and weight status.
      IMAAT was higher in children with MAFLD (44.3%) (Fig. 1A, ES: 0.39), and in those with light (Fig.1B, ES: 0.32) and moderate-high MAFLD (Fig. 1B, ES: 0.65) than in those without. IMAAT was similar in boys and girls (Fig. 1C, ES: 0.01), while children with obesity presented higher IMAAT than those who were overweight (Fig. 1D, ES: 0.63).
      Figure thumbnail gr1
      Fig. 1IMAAT levels based on the presence MAFLD, steatosis severity, sex and weight status.
      (A) Children with and without MAFLD. (B) MAFLD spectrum (i.e., Non-MAFLD: hepatic fat <5%, light MAFLD: hepatic fat between 5% and 8%, moderate to high MAFLD: hepatic fat ≥9%). (C) MAFLD in girls and boys. (D) MAFLD in children who are overweight and those who are obese. All data are based on Gardner-Altman plots
      • Ho J.
      • Tumkaya T.
      • Aryal S.
      • Choi H.
      • Claridge-Chang A.
      Moving beyond P values: data analysis with estimation graphics.
      ,
      • Gardner M.J.
      • Altman D.G.
      Confidence intervals rather than P values: estimation rather than hypothesis testing.
      which show a representation of observed values by the 2-group comparison and its effect size (black circle), and 95% CIs. The curve indicates the resampled distribution of the effect size given the observed data. IMAAT, intermuscular abdominal fat fraction; MAFLD, metabolic dysfunction-associated fatty liver disease.
      Our results in children concur with those reported by Nachit et al.
      • Nachit M.
      • Kwanten W.J.
      • Thissen J.-P.
      • Op de Beeck B.
      • Van Gaal L.
      • Vonghia L.
      • et al.
      Muscle fat content is strongly associated with NASH: a longitudinal study in patients with morbid obesity.
      in adults with morbid obesity, and suggest that fatty infiltration of muscle mass could contribute to the physiopathology of MAFLD from childhood. Nachit et al.
      • Nachit M.
      • Kwanten W.J.
      • Thissen J.-P.
      • Op de Beeck B.
      • Van Gaal L.
      • Vonghia L.
      • et al.
      Muscle fat content is strongly associated with NASH: a longitudinal study in patients with morbid obesity.
      also observed that non-alcoholic steatohepatitis improved in those patients who significantly decreased muscle fat content, suggesting that the reduction of fat infiltration in the muscle may be a relevant therapeutic target for patients with MAFLD. Muscle fat content is sensitive to exercise-based interventions,
      • Laurens C.
      • de Glisezinski I.
      • Larrouy D.
      • Harant I.
      • Moro C.
      Influence of acute and chronic exercise on abdominal fat lipolysis: an update.
      and could therefore be a strategy to improve MAFLD. Further studies should test this hypothesis, particularly in children where the prevalence of MAFLD is alarming.
      • Yu E.L.
      • Schwimmer J.B.
      Epidemiology of pediatric nonalcoholic fatty liver disease.
      In conclusion, our data extend previous observations reported in adults with morbid obesity
      • Nachit M.
      • Kwanten W.J.
      • Thissen J.-P.
      • Op de Beeck B.
      • Van Gaal L.
      • Vonghia L.
      • et al.
      Muscle fat content is strongly associated with NASH: a longitudinal study in patients with morbid obesity.
      to children who are overweight/obese, and support the screening of muscle fat as a potential marker of the presence and progression of MAFLD that might unravel new relevant therapeutic targets. Further studies are needed to confirm our findings.

      Financial support

      This project was funded by the Spanish Ministry of Health “Fondos de Investigación Sanitaria del Instituto de Salud Carlos III” (PI13/01335), the Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R), and by EU Fondos Estructurales de la Unión Europea (FEDER) funds (“Una manera de hacer Europa”). Support was also provided by the Department of Economic Development of the Government of Navarra (0011-1365-2019-000152) and co-funded by EU Fondos Estructurales de la Unión Europea (FEDER) funds ("Una manera de hacer Europa"). CC-S is supported by the Spanish Ministry of Science and Innovation (FJC2018-037925-I).

      Authors’ contributions

      CC-S.: conception of the study, analysed the data, and drafted the manuscript; FI, AV, RC: acquisition, analysis, and interpretation of the data, and critically review the manuscript. IL: conception of the study, analysed and interpretation of the data, and critically review the manuscript. The authors declare they have seen and approved the final version of the manuscript.

      Conflict of interest

      The authors declare no conflicts of interest that pertain to this work.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following is the supplementary data to this article:

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        Muscle fat content is strongly associated with NASH: a longitudinal study in patients with morbid obesity.
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        • Medrano M.
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        Effects of exercise in addition to a family-based lifestyle intervention program on hepatic fat in children with overweight.
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        Confidence intervals rather than P values: estimation rather than hypothesis testing.
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