Differential response to a 6-month energy-restricted treatment depending on SH2B1 rs7359397 variant in NAFLD subjects: Fatty Liver in Obesity (FLiO) Study.

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.

Effects of a 6-month dietary-induced weight loss on erythrocyte membrane omega-3 fatty acids and hepatic status of subjects with nonalcoholic fatty liver disease: The Fatty Liver in Obesity study.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) have been suggested as important biomolecules in the management of nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: This study aimed to evaluate the effect of 6-month weight loss diets on erythrocyte membrane omega-3 PUFA composition of NAFLD adults, and to evaluate the potential relationship between erythrocyte membrane omega-3 PUFAs and hepatic health markers. METHODS: In this secondary analysis of the Fatty Liver in Obesity study, erythrocyte membranes were analyzed by gas chromatography in 54 subjects with liver steatosis detected by ultrasonography who achieved a weight loss >5% after the follow-up. Baseline and 6-month evaluation included hepatic acoustic radiation force impulse elastography and magnetic resonance imaging, anthropometry, body composition, and biochemical determinations. RESULTS: After the follow-up, α-linolenic acid (ALA) proportion significantly increased in erythrocyte membranes, whereas eicosapentaenoic acid (EPA) showed no statistical difference and docosapentaenoic acid decreased. Both the changes in erythrocyte membrane ALA and EPA were positively associated with dietary ALA. Regression analyses evidenced that the changes in erythrocyte membrane ALA and EPA were inversely associated with the changes in liver stiffness and liver iron content, respectively. CONCLUSION: The adherence to weight loss strategies for 6 months led to changes in erythrocyte membrane omega-3 PUFA composition, which in turn were associated with changes in hepatic markers, suggesting that these fatty acids accompany the improvements in the liver during a dietary treatment. These findings show that beyond weight loss, the composition of the diet has an important role in the management of NAFLD.