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Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. The pathogenesis of NAFLD is complex; available data reveal that genetics and ascribed interactions with environmental factors may play an important role in the development of this morbid condition. The purpose of this investigation was to assess genetic and non-genetic determinants putatively involved in the onset and progression of NAFLD after a 6-month weight loss nutritional treatment. A group of 86 overweight/obese subjects with NAFLD from the Fatty Liver in Obesity (FLiO) study were enrolled and metabolically evaluated at baseline and after 6 months. A pre-designed panel of 95 genetic variants related to obesity and weight loss was applied and analyzed. Three genetic risk scores (GRS) concerning the improvement on hepatic health evaluated by minimally invasive methods such as the fatty liver index (FLI) (GRSFLI), lipidomic-OWLiver®-test (GRSOWL) and magnetic resonance imaging (MRI) (GRSMRI), were derived by adding the risk alleles genotypes. Body composition, liver injury-related markers and dietary intake were also monitored. Overall, 23 SNPs were independently associated with the change in FLI, 16 SNPs with OWLiver®-test and 8 SNPs with MRI, which were specific for every diagnosis tool. After adjusting for gender, age and other related predictors (insulin resistance, inflammatory biomarkers and dietary intake at baseline) the calculated GRSFLI, GRSOWL and GRSMRI were major contributors of the improvement in hepatic status. Thus, fitted linear regression models showed a variance of 53% (adj. R2 = 0.53) in hepatic functionality (FLI), 16% (adj. R2 = 0.16) in lipidomic metabolism (OWLiver®-test) and 34% (adj. R2 = 0.34) in liver fat content (MRI). These results demonstrate that three different genetic scores can be useful for the personalized management of NAFLD, whose treatment must rely on specific dietary recommendations guided by the measurement of specific genetic biomarkers.
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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.
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Enfermedad del Hígado Graso no Alcohólico , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Composición Corporal , Humanos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/genética , Obesidad/metabolismo , Sobrepeso/genética , Sobrepeso/metabolismoRESUMEN
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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Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Adulto , Aminoácidos , Aminoácidos de Cadena Ramificada , Ingestión de Alimentos , Humanos , Hígado , Obesidad/complicacionesRESUMEN
The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (ß = 19.21; p ≤ 0.001), liver fat content (ß = 8.70; p = 0.008), and hepatic iron (ß = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT).
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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.
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Dieta , Membrana Eritrocítica/metabolismo , Ácidos Grasos Omega-3/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/complicaciones , Pérdida de Peso , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. Some genetic variants might be involved in the progression of this disease. The study hypothesized that individuals with the rs7359397 T allele have a higher risk of developing severe stages of NAFLD compared with non-carriers where dietary intake according to genotypes could have a key role on the pathogenesis of the disease. SH2B1 genetic variant was genotyped in 110 overweight/obese subjects with NAFLD. Imaging techniques, lipidomic analysis and blood liver biomarkers were performed. Body composition, general biochemical and dietary variables were also determined. The SH2B1 risk genotype was associated with higher HOMA-IR p = 0.001; and Fatty Liver Index (FLI) p = 0.032. Higher protein consumption (p = 0.028), less mono-unsaturated fatty acid and fiber intake (p = 0.045 and p = 0.049, respectively), was also referred to in risk allele genotype. Lipidomic analysis showed that T allele carriers presented a higher frequency of non-alcoholic steatohepatitis (NASH) (69.1% vs. 44.4%; p = 0.006). In the genotype risk group, adjusted logistic regression models indicated a higher risk of developing an advanced stage of NAFLD measured by FLI (OR 2.91) and ultrasonography (OR 4.15). Multinomial logistic regression models showed that risk allele carriers had higher liver fat accumulation risk (RRR 3.93) and an increased risk of NASH (RRR 7.88). Consequently, subjects carrying the T allele were associated with a higher risk of developing a severe stage of NAFLD. These results support the importance of considering genetic predisposition in combination with a healthy dietary pattern in the personalized evaluation and management of NAFLD.
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Proteínas Adaptadoras Transductoras de Señales/genética , Hígado Graso/etiología , Hígado Graso/genética , Estudios de Asociación Genética , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad/genética , Polimorfismo Genético , Alelos , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/etiología , Riesgo , Índice de Severidad de la EnfermedadRESUMEN
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity.
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Restricción Calórica , Dieta Mediterránea , Enfermedad del Hígado Graso no Alcohólico , Obesidad , Adulto , Anciano , Anciano de 80 o más Años , Ejercicio Físico , Femenino , Humanos , Hígado/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/complicaciones , Obesidad/dietoterapia , Obesidad/fisiopatología , Pérdida de Peso/fisiologíaRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Obesity and unhealthy dietary habits are described as risk factors for NAFLD. The aim of this study was to investigate the association between the consumption of different animal protein sources and hepatic status in NAFLD adults. A total of 112 overweight/obese participants with NAFLD from Fatty Liver in Obesity (FLiO) study were evaluated at baseline. Diet, body composition, and biochemical variables were evaluated. Hepatic status was also assessed by Magnetic Resonance Imaging, ultrasonography, and elastography. Red meat consumption showed a positive relationship with liver iron content (r = 0.224; p = 0.021) and ferritin concentration (r = 0.196; p = 0.037). Processed meat consumption exhibited a positive association with liver iron content (r = 0.308; p = 0.001), which was also found in the quantile regression (ß = 0.079; p = 0.028). Fish consumption was related with lower concentration of ferritin (r = -0.200; p = 0.034). This association was further evidenced in the regression model (ß = -0.720; p = 0.033). These findings suggest that the consumption of different animal protein sources differentially impact on liver status in obese subjects with NAFLD, showing fish consumption as a healthier alternative for towards NAFLD features.
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Proteínas en la Dieta/administración & dosificación , Carne , Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Animales , Composición Corporal , Índice de Masa Corporal , Dieta Saludable , Conducta Alimentaria , Femenino , Ferritinas/sangre , Peces , Manipulación de Alimentos , Humanos , Hierro/análisis , Hígado/química , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/fisiopatología , Carne Roja , Factores de RiesgoRESUMEN
The relevance of sleep patterns in the onset or evolution of nonalcoholic fatty liver disease (NAFLD) is still poorly understood. Our aim was to investigate the association between sleep characteristics and hepatic status indicators in obese people with NAFLD compared to normal weight non-NAFLD controls. Ninety-four overweight or obese patients with NAFLD and 40 non-NAFLD normal weight controls assessed by abdominal ultrasonography were enrolled. Hepatic status evaluation considered liver stiffness determined by Acoustic Radiation Force Impulse elastography (ARFI) and transaminases. Additionally, anthropometric measurements, clinical characteristics, and biochemical profiles were determined. Sleep features were evaluated using the Pittsburgh Sleep Quality Index (PSQI). Hepatic status parameters, anthropometric measurements, and clinical and biochemical markers differed significantly in NAFLD subjects compared to controls, as well as sleep efficiency, sleep disturbance score, and sleep quality score. In the NAFLD group, a higher prevalence of short sleep duration (p = 0.005) and poor sleep quality (p = 0.041) were found. Multivariate-adjusted odds ratio (95% confidence interval) for NAFLD considering sleep disturbance was 1.59 (1.11â»2.28). Regression models that included either sleep disturbance or sleep quality predicted up to 20.3% and 20.4% of the variability of liver stiffness, respectively, and after adjusting for potential confounders. Current findings suggest that sleep disruption may be contributing to the pathogenesis of NAFLD as well as the alteration of the liver may be affecting sleep patterns. Consequently, sleep characteristics may be added to the list of modifiable behaviors to consider in health promotion strategies and in the prevention and management of NAFLD.
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Índice de Masa Corporal , Peso Corporal , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/complicaciones , Trastornos del Sueño-Vigilia/complicaciones , Sueño , Adulto , Biomarcadores , Estudios de Casos y Controles , Femenino , Dureza , Humanos , Hígado/enzimología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/etiología , Oportunidad Relativa , Sobrepeso , Transaminasas/sangreRESUMEN
BACKGROUND: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on dietâ»disease relationships. The aim of this study was to evaluate potential associations of dietary TAC, GI, and GL with variables related to nutritive status and insulin resistance (IR) risk in cardiometabolic subjects. METHODS: A total of 112 overweight or obese adults (age: 50.8 ± 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ), which was also used to calculate the dietary TAC, GI, and GL. Anthropometrics, blood pressure, body composition by dual-energy X-ray absorptiometry (DXA), glycemic and lipid profiles, C-reactive protein (CRP), as well as fatty liver quantification by magnetic resonance imaging (MRI) were assessed. RESULTS: Subjects with higher values of TAC had significantly lower circulating insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR). Participants with higher values of HOMA-IR showed significantly higher GI and GL. Correlation analyses showed relevant inverse associations of GI and GL with TAC. A regression model evidenced a relationship of HOMA-IR with TAC, GI, and GL. CONCLUSION: This data reinforces the concept that dietary TAC, GI, and GL are potential markers of diet quality, which have an impact on the susceptible population with a cardiometabolic risk profile.