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Dietary intake of specific amino acids and liver status in subjects with nonalcoholic fatty liver disease: fatty liver in obesity (FLiO) study

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Abstract

Purpose

Identification of dietary factors involved in the development and progression of nonalcoholic fatty liver disease (NAFLD) is relevant to the current epidemics of the disease. Dietary amino acids appear to play a key role in the onset and progression of NAFLD. The aim of this study was to analyze potential associations between specific dietary amino acids and variables related to glucose metabolism and hepatic status in adults with overweight/obesity and NAFLD.

Methods

One hundred and twelve individuals from the Fatty Liver in Obesity (FLiO) study were evaluated. Liver assessment was carried out by ultrasonography, magnetic resonance imaging and analysis of biochemical parameters. Dietary amino acid intake (aromatic amino acids (AAA); branched-chain amino acids (BCAA); sulfur amino acids (SAA)) was estimated by means of a validated 137-item food frequency questionnaire.

Results

Higher consumption of these amino acids was associated with worse hepatic health. Multiple adjusted regression models confirmed that dietary AAA, BCAA and SAA were positively associated with liver fat content. AAA and BCAA were positively associated with liver iron concentration. Regarding ferritin levels, a positive association was found with BCAA. Dietary intake of these amino acids was positively correlated with glucose metabolism (glycated hemoglobin, triglyceride and glucose index) although the significance disappeared when potential confounders were included in the model.

Conclusion

These findings suggest that the consumption of specific dietary amino acids might negatively impact on liver status and, to a lesser extent on glucose metabolism in subjects with overweight/obesity and NAFLD. A control of specific dietary amino acid composition should be considered in the management of NAFLD and associated insulin resistance. NCT03183193; June 2017.

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Abbreviations

AAA:

Aromatic amino acids

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

BAT:

Brown adipose tissue

BCAA:

Branched-chain amino acids

BMI:

Body mass index

CMIA:

Chemiluminescent microparticle immunoassay

CVD:

Cardiovascular diseases

ELISA:

Enzyme-linked immunosorbent assay

FFA:

Free fatty acids

FFQ:

Food frequency questionnaire

GGT:

Gamma glutamyl transferase

HbA1c:

Glycated hemoglobin

HDL-c:

High-density lipoprotein cholesterol

HOMA-IR:

Homeostatic Model Assessment of Insulin Resistance

IDF:

International Diabetes Federation

IR:

Insulin resistance

IRS-1:

Insulin receptor substrate-1

LDL-c:

Low-density lipoprotein cholesterol

MetS:

Metabolic syndrome

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

SAA:

Sulfur amino acids

T2D:

Type 2 diabetes

TG:

Triglycerides

TyG index:

Triglyceride–glucose index

WAT:

White adipose tissue

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Acknowledgements

The authors are very grateful to all the participants of the study. The authors wish to express their gratitude to the Government of Navarra, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), and Fundació La Marató de TV3 for the financial support. Cristina Galarregui appreciates the predoctoral grant received from Congelados de Navarra, Government of Navarra, and Ministerio de Educación, Cultura y Deporte. Thanks are given to all the staff (www.clinicaltrials.gov; NCT03183193) for their contribution to FLiO project. Helen Hermana M. Hermsdorff and Josefina Bressan are CNPq Research Productivity fellows.

Funding

This work was supported by the Health Department of the Government of Navarra [61/2015], CIBERobn (Physiopathology of Obesity and Nutrition) [CB12/03/3002] and Fundació La Marató de TV3 [201630.10]. Cristina Galarregui was partially supported by fellowships from Congelados de Navarra, Government of Navarra, and Ministerio de Educación, Cultura y Deporte [FPU17/06330].

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Author notes

  1. M. Angeles Zulet and Itziar Abete contributed equally to this work.

Authors and Affiliations

  1. Department of Nutrition, Food Sciences and Physiology and Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, Irunlarrea 1, 31008, Pamplona, Spain

    Cristina Galarregui, Irene Cantero, Bertha Araceli Marin-Alejandre, J. Alfredo Martínez, M. Angeles Zulet & Itziar Abete

  2. Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain

    J. Ignacio Monreal, Mariana Elorz, Alberto Benito-Boillos, José Ignacio Herrero, Víctor de la O, Miguel Ruiz-Canela, J. Alfredo Martínez, M. Angeles Zulet & Itziar Abete

  3. Clinical Chemistry Department, Clinica Universidad de Navarra, 31008, Pamplona, Spain

    J. Ignacio Monreal

  4. Department of Radiology, Clinica Universidad de Navarra, 31008, Pamplona, Spain

    Mariana Elorz & Alberto Benito-Boillos

  5. Liver Unit, Clinica Universidad de Navarra, 31008, Pamplona, Spain

    José Ignacio Herrero

  6. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029, Madrid, Spain

    José Ignacio Herrero

  7. Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, 31008, Pamplona, Spain

    Víctor de la O & Miguel Ruiz-Canela

  8. Biomedical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029, Madrid, Spain

    Miguel Ruiz-Canela, Josep A. Tur, J. Alfredo Martínez, M. Angeles Zulet & Itziar Abete

  9. Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, 36570-900, Brazil

    Helen Hermana M. Hermsdorff & Josefina Bressan

  10. Research Group On Community Nutrition and Oxidative Stress, University of Balearic Islands and Balearic Islands Institute for Health Research (IDISBA), 07122, Palma, Spain

    Josep A. Tur

Authors
  1. Cristina Galarregui
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  2. Irene Cantero
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Contributions

CG: conceptualization, data curation, formal analysis, investigation, methodology, supervision, validation, visualization, roles/writing—original draft; writing—review and editing. IC: conceptualization and methodology. BAM-A: conceptualization, data curation, and methodology. JIM: conceptualization and methodology. ME: conceptualization and methodology. ABB: conceptualization and ethodology. José IH: conceptualization and methodology. VlO: conceptualization and methodology. MR-C: conceptualization and methodology. HHMH: conceptualization and methodology. JB: conceptualization and methodology. JAT: conceptualization, formal analysis, funding acquisition, methodology, and project administration. JAM: conceptualization, cata curation, formal analysis, funding acquisition, investigation, methodology, project administration, supervision, validation, visualization, roles/writing—original draft, and writing—review and editing. MAZ: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, supervision, validation, visualization, roles/writing—original draft, writing—review and editing. IA: conceptualization, data curation, formal analysis, investigation, methodology, project administration, supervision, validation, visualization, roles/writing—original draft, writing—review and editing.

Corresponding authors

Correspondence to M. Angeles Zulet or Itziar Abete.

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Ethical standards

The present study has been approved by the Research Ethics Committee of the University of Navarra on 24 April 2015 (ref. 54/2015).and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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All participants of the present study gave their informed consent prior to their inclusion in the study.

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All data and materials support their published claims and comply with field standards.

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Galarregui, C., Cantero, I., Marin-Alejandre, B.A. et al. Dietary intake of specific amino acids and liver status in subjects with nonalcoholic fatty liver disease: fatty liver in obesity (FLiO) study. Eur J Nutr 60, 1769–1780 (2021). https://doi.org/10.1007/s00394-020-02370-6

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