Fatty Liver in Obesity: Long-lifestyle Follow-up (FLiO)

This project is framed within the promotion of health and lifestyles and, specifically, in liver disorder linked to obesity (FLiO: Fatty Liver in Obesity). The investigation addresses a randomized, parallel, long-term personalized nutritional intervention with two strategies: 1) Control diet based on American Heart Association (AHA); 2) Fatty Liver in Obesity (FLiO) diet based on previous results (RESMENA project).The diet is based on macronutrient distribution, quality and quantity, and is characterized by a low glycemic load, high adherence to the Mediterranean diet and a high antioxidant capacity, with the inclusion of anti-inflammatory foods. It also takes into account the distribution of food throughout the day, number of meals, portion sizes, timing of meal, individual needs, dietary behavior (behavioral therapy: eat slowly, teach what to buy, what to eat, when to eat). The participants are instructed to follow this strategy. This strategy (RESMENA) was even more effective than AHA after 6 months follow-up, in terms of significant reduction of abdominal fat and blood glucose level. In addition, this diet had beneficial effects for participants who were obese and had values of altered glucose, reducing significantly in RESMENA participants LDL-oxidized marker. These results are very important to apply in the present investigation since that patients with NAFLD are commonly insulin resistant. Both strategies were designed within a hypocaloric dietary pattern (-30%) in order to achieve the American Association for the Study of Liver Diseases (AASLD) recommendations for the management of non-alcoholic liver disease (loss of at least 3-5% of body weight appears necessary to improve steatosis, but a greater weight loss, up to 10%, may be needed to improve necroinflammation). At this time the participants are individually supervised and encouraged to follow with the dietary planning instructions assigned. Furthermore, at baseline, 6, 12 and 24 months anticipated variables are obtained. Both dietary groups receive routine control (weight, body composition, strategy adherence) and dietary advice daily by phone (if they need help) and face to face at the time of routine control. In order to get a integral lifestyle intervention, all participants will be encouraged to follow a healthy lifestyle. Thus, physical activity will be recorded in each dietary group. The specific tasks: 1. To recruit and select patients with the adequate characteristics to validate the conclusions reached. 2. To develop and adequately transmit to each patient a personalized strategy according to the group randomly assigned ( AASLD vs FLiO strategy). 3. To check the degree of adherence to the strategy set by regular monitoring: semiquantitative questionnaires of food consumption frequency, pedometers, accelerometers, weight control, satiety. 4. To assess the effect of each strategy on body composition (weight, waist circumference, body fat, muscle mass, bone mineral density), physical status, general biochemistry (lipid profile, glycaemic profile, albumin, blood count, transaminases), specific biomarkers/metabolites in blood or urine (inflammation, oxidative stress, liver damage, appetite, psychological status), quality of life and related factors (anxiety, depression and sleep). 5. To check the evolution of the liver damage, using non-invasive techniques (ultrasound, elastography and magnetic resonance imaging (MRI), metabolomics analysis) and calculating different validated liver scores from the data obtained with each strategy. 6. To compare the effectiveness of strategies, considering not only the ability to decrease body fat, but also other risk factors present in the NAFLD patient such as insulin resistance and cardiovascular risk, which will result in improvement of liver damage. 7. To analyze SNPs (DNA from oral epithelial cells) and the association with NAFLD (diagnosis and response to the strategies). 8. To study gene expression (mRNAs) and microRNAs in white blood cells for identifying biomarkers of diagnosis and response to dietary strategy. 9. To analyze gene DNA methylation patterns in white blood cells for identifying biomarkers of diagnosis and response to dietary strategy. 10. To describe the intestinal microbiota composition by 16s sequencing at baseline and after nutritional intervention for diagnosis and response.