Itziar Abete1,2,3,4, M Angeles Zulet5,6,7,8, Nuria Perez-Diaz-Del-Campo9,10, Bertha Araceli Marin-Alejandre9,10, Irene Cantero9,10, J Ignacio Monreal11,12, Mariana Elorz11,13, José Ignacio Herrero11,14,15, Alberto Benito-Boillos11,13, Jose I Riezu-Boj9,10,11, Fermín I Milagro9,10,11,16, Josep A Tur16,17, J Alfredo Martinez9,10,11,16. 1. Department of Nutrition, Food Sciences and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008, Pamplona, Spain. iabetego@unav.es. 2. Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008, Pamplona, Spain. iabetego@unav.es. 3. Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain. iabetego@unav.es. 4. Biochemical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029, Madrid, Spain. iabetego@unav.es. 5. Department of Nutrition, Food Sciences and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008, Pamplona, Spain. mazulet@unav.es. 6. Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008, Pamplona, Spain. mazulet@unav.es. 7. Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain. mazulet@unav.es. 8. Biochemical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029, Madrid, Spain. mazulet@unav.es. 9. Department of Nutrition, Food Sciences and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008, Pamplona, Spain. 10. Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008, Pamplona, Spain. 11. Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain. 12. Clinical Chemistry Department, Clínica Universidad de Navarra, 31008, Pamplona, Spain. 13. Department of Radiology, Clínica Universidad de Navarra, 31008, Pamplona, Spain. 14. Liver Unit, Clínica Universidad de Navarra, 31008, Pamplona, Spain. 15. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029, Madrid, Spain. 16. Biochemical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029, Madrid, Spain. 17. Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands & Balearic Islands Institute for Health Research (IDISBA), 07122, Palma, Spain.
Abstract
PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is worldwide recognized as the most common cause of chronic liver disease. Current NAFLD clinical management relies on lifestyle change, nevertheless, the importance of the genetic make-up on liver damage and the possible interactions with diet are still poorly understood. The aim of the study was to evaluate the influence of the SH2B1 rs7359397 genetic variant on changes in body composition, metabolic status and liver health after 6-month energy-restricted treatment in overweight/obese subjects with NAFLD. In addition, gene-treatment interactions over the course of the intervention were examined. METHODS: The SH2B1 genetic variant was genotyped in 86 overweight/obese subjects with NAFLD from the FLiO study (Fatty Liver in Obesity study). Subjects were metabolically evaluated at baseline and at 6-months. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, a lipidomic test (OWL®-test) and specific blood liver biomarkers. Additionally, body composition, general biochemical markers and dietary intake were determined. RESULTS: Both genotypes significantly improved their body composition, general metabolic status and liver health after following an energy-restricted strategy. Liver imaging techniques showed a greater decrease in liver fat content (- 44.3%, p < 0.001) and in serum ferritin levels (p < 0.001) in the carriers of the T allele after the intervention. Moreover, lipidomic analysis, revealed a higher improvement in liver status when comparing risk vs. no-risk genotype (p = 0.006 vs. p = 0.926, respectively). Gene-treatment interactions showed an increase in fiber intake and omega-3 fatty acid in risk genotype (p interaction = 0.056 and p interaction = 0.053, respectively), while a significant increase in MedDiet score was observed in both genotype groups (p = 0.020). Moreover, no-risk genotype presented a relevant decrease in hepatic iron as well as in MUFA intake (p = 0.047 and p = 0.034, respectively). CONCLUSION: Subjects carrying the T allele of the rs7359397 polymorphism may benefit more in terms of hepatic health and liver status when prescribed an energy-restricted treatment, where a Mediterranean dietary pattern rich in fiber and other components such as omega-3 fatty acids might boost the benefits. TRIAL REGISTRATION: The Fatty Liver in Obesity was approved by the Research Ethics Committee of the University of Navarra and retrospectively registered (NCT03183193; www.clinicaltrials.gov ); June 2017.
PURPOSE:Non-alcoholic fatty liver disease (NAFLD) is worldwide recognized as the most common cause of chronic liver disease. Current NAFLD clinical management relies on lifestyle change, nevertheless, the importance of the genetic make-up on liver damage and the possible interactions with diet are still poorly understood. The aim of the study was to evaluate the influence of the SH2B1rs7359397 genetic variant on changes in body composition, metabolic status and liver health after 6-month energy-restricted treatment in overweight/obese subjects with NAFLD. In addition, gene-treatment interactions over the course of the intervention were examined. METHODS: The SH2B1 genetic variant was genotyped in 86 overweight/obese subjects with NAFLD from the FLiO study (Fatty Liver in Obesity study). Subjects were metabolically evaluated at baseline and at 6-months. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, a lipidomic test (OWL®-test) and specific blood liver biomarkers. Additionally, body composition, general biochemical markers and dietary intake were determined. RESULTS: Both genotypes significantly improved their body composition, general metabolic status and liver health after following an energy-restricted strategy. Liver imaging techniques showed a greater decrease in liver fat content (- 44.3%, p < 0.001) and in serum ferritin levels (p < 0.001) in the carriers of the T allele after the intervention. Moreover, lipidomic analysis, revealed a higher improvement in liver status when comparing risk vs. no-risk genotype (p = 0.006 vs. p = 0.926, respectively). Gene-treatment interactions showed an increase in fiber intake and omega-3 fatty acid in risk genotype (p interaction = 0.056 and p interaction = 0.053, respectively), while a significant increase in MedDiet score was observed in both genotype groups (p = 0.020). Moreover, no-risk genotype presented a relevant decrease in hepatic iron as well as in MUFA intake (p = 0.047 and p = 0.034, respectively). CONCLUSION: Subjects carrying the T allele of the rs7359397 polymorphism may benefit more in terms of hepatic health and liver status when prescribed an energy-restricted treatment, where a Mediterranean dietary pattern rich in fiber and other components such as omega-3 fatty acids might boost the benefits. TRIAL REGISTRATION: The Fatty Liver in Obesity was approved by the Research Ethics Committee of the University of Navarra and retrospectively registered (NCT03183193; www.clinicaltrials.gov ); June 2017.
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