Changes in lysophospholipids and liver status after weight loss: the RESMENA study

Background: Obesity and comorbidities such as non-alcoholic fatty liver disease (NAFLD) are major public health burdens. Alterations in lipid metabolism are involved in hepatic diseases. The objective of this study was to assess the influence of weight loss on lysophospholipid (LP) metabolism and liver status in obese subjects as well as to provide new evidence regarding the interaction of LP metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage. Methods: Thirty-three subjects from the RESMENA (Reduction of Metabolic Syndrome in Navarra, NCT01087086) study were selected based on their Fatty Liver Index (FLI). Plasma lipid species (lysophosphatidilcholine: LPC, lysophosphatidilethanolamines: LPE and lysophosphatidylinositols: LPI specifically) were determined by LC-MS, while waist circumference (WC) and other non-invasive liver markers such as, FLI and BAAT scores as well as dietary records, anthropometrical measurements, body composition by DXA and other metabolic determinants were analyzed before and after a six-month hypocaloric nutritional intervention. Results: Computed Z-scores of total LP (LPC, LPE, and LPI) were significantly decreased after 6-months of following a hypocaloric diet. Specifically, LPC14:0, LPC15:0, LPC16:1, LPC18:4, LPC20:4, showed clear relationships with weight loss. Changes in FLI score, WC and BAAT score revealed associations with general changes in LPC score. Interestingly the BAAT score was statistically associated with the LPC score after adjustment for weight loss. Conclusion: The lipidomic LPC profile analysis revealed a generalized decrease in circulating lysophospholipids after weight loss. The involvement of particular LP in liver metabolism and obesity merit further attention, as some of these specific non-invasive liver markers were reduced independently of weight loss

Association between Different Animal Protein Sources and Liver Status in Obese Subjects with Non-Alcoholic Fatty Liver Disease: Fatty Liver in Obesity (FLiO) Study

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 (β = 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 (β = -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

Interplay of glycemic index, glycemic load, and dietary antioxidant capacity with insulin resistance in subjects with a cardiometabolic risk profile

Background: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on diet–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

Predictive value of serum ferritin in combination with alanine aminotransferase and glucose levels for noninvasive assessment of NAFLD: Fatty liver in obesity (FLiO) study

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) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 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)

Association of the SH2B1 rs7359397 gene polymorphism with steatosis severity in subjects with obesity and non-alcoholic fatty liver disease

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 equal 0.001; and Fatty Liver Index (FLI) p equal 0.032. Higher protein consumption (p equal 0.028), less mono-unsaturated fatty acid and fiber intake (p equal 0.045 and p equal 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) (69.1/100 vs. 44.4/100; p equal 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

The Metabolic and Hepatic Impact of Two Personalized Dietary Strategies in Subjects with Obesity and Nonalcoholic Fatty Liver Disease: The Fatty Liver in Obesity (FLiO) Randomized Controlled Trial

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

Association between sleep disturbances and liver status in obese subjects with nonalcoholic fatty liver disease: a comparison with healthy controls

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 (1.11–2.28). 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

Underlying metabolic processes behind non-alcoholic fatty liver disease in population with metabolic syndrome features: nutritional status and non-invasive liver tools

Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in the Western world, affecting up to 20-30% of the general adult population. It is a growing public health problem, because of the increasing prevalence of the pathologies that contribute to its development such as obesity and inflammation status. The diagnostic method of choice for NAFLD is liver biopsy, but since it is a long-standing disease, it is difficult to follow large population groups through serial biopsies. Therefore, it is necessary to identify noninvasive liver damage tools that facilitate the diagnosis and prognosis of the disease and allow for the establishment of a follow-up protocol that prevents progression to severe stages of NAFLD. Moreover, the main therapeutic basis is the modification of lifestyle through diet and exercise In this context, this research work aimed: 1) to assess the possible association between a validated Dietary Inflammatory Index (DII) and specific dietary components with suitable non-invasive markers of liver status in overweight/obese subjects with cardiovascular risk; 2) to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in overweight/obese individuals with features of metabolic syndrome after six months of follow-up and to assess the role of fiber content in metabolic outcomes; 3) to assess the influence of weight loss on lysophospholipid metabolism and liver status in overweight/obese subjects as well as to provide new evidence regarding the interaction of lysophospholipids metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage; 4) to analyze the response of FGF-21 after a weight loss intervention and the relationships with other putative inflammatory liver biomarkers; 5) to evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging (MRI) in adults subjects with NAFLD. In relation with the first objective, the results of this chapter evidended that the consumption of an anti-inflammatory dietary pattern might contribute to the reduction of obesity and related comorbidities, especially NAFLD through precision nutrition guidelines. Concerning the second objective, we concluded that the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction is a good choice the management of obese patients suffering from NAFLD. The third chapter suggested a generalized decrease in circulating lysophospholipids (LP), particularly lysophosphatidylcholine, after a weight loss intervention in a population with metabolic syndrome features. Changes in fatty liver index, waist circumference and BAAT score revealed positive association with lysophosphatidylcholine score. The involvement of particular LP in liver metabolism and obesity merits further attention. The fourth chapter revealed that FGF-21 changes exhibit a great association with non-alcoholic fatty liver inflammation, M30 fragment and PAI-I, independently of weight loss. These findings suggest that FGF-21 is involved in the obesity-inflammation-liver process. Finally, in relation to the fifth objective we concluded that ultrasonography, a metabolomic test and a panel combination including routine blood markers linked to insulin resistance showed the highest associations with MRI, which is considered the gold standard for non-invasive liver fat content assessment, suggesting these tools could contribute to the diagnosis and prognosis of NAFLD

Underlying metabolic processes behind non-alcoholic fatty liver disease in population with metabolic syndrome features: nutritional status and non-invasive liver tools

Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in the Western world, affecting up to 20-30% of the general adult population. It is a growing public health problem, because of the increasing prevalence of the pathologies that contribute to its development such as obesity and inflammation status. The diagnostic method of choice for NAFLD is liver biopsy, but since it is a long-standing disease, it is difficult to follow large population groups through serial biopsies. Therefore, it is necessary to identify noninvasive liver damage tools that facilitate the diagnosis and prognosis of the disease and allow for the establishment of a follow-up protocol that prevents progression to severe stages of NAFLD. Moreover, the main therapeutic basis is the modification of lifestyle through diet and exercise In this context, this research work aimed: 1) to assess the possible association between a validated Dietary Inflammatory Index (DII) and specific dietary components with suitable non-invasive markers of liver status in overweight/obese subjects with cardiovascular risk; 2) to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in overweight/obese individuals with features of metabolic syndrome after six months of follow-up and to assess the role of fiber content in metabolic outcomes; 3) to assess the influence of weight loss on lysophospholipid metabolism and liver status in overweight/obese subjects as well as to provide new evidence regarding the interaction of lysophospholipids metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage; 4) to analyze the response of FGF-21 after a weight loss intervention and the relationships with other putative inflammatory liver biomarkers; 5) to evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging (MRI) in adults subjects with NAFLD. In relation with the first objective, the results of this chapter evidended that the consumption of an anti-inflammatory dietary pattern might contribute to the reduction of obesity and related comorbidities, especially NAFLD through precision nutrition guidelines. Concerning the second objective, we concluded that the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction is a good choice the management of obese patients suffering from NAFLD. The third chapter suggested a generalized decrease in circulating lysophospholipids (LP), particularly lysophosphatidylcholine, after a weight loss intervention in a population with metabolic syndrome features. Changes in fatty liver index, waist circumference and BAAT score revealed positive association with lysophosphatidylcholine score. The involvement of particular LP in liver metabolism and obesity merits further attention. The fourth chapter revealed that FGF-21 changes exhibit a great association with non-alcoholic fatty liver inflammation, M30 fragment and PAI-I, independently of weight loss. These findings suggest that FGF-21 is involved in the obesity-inflammation-liver process. Finally, in relation to the fifth objective we concluded that ultrasonography, a metabolomic test and a panel combination including routine blood markers linked to insulin resistance showed the highest associations with MRI, which is considered the gold standard for non-invasive liver fat content assessment, suggesting these tools could contribute to the diagnosis and prognosis of NAFLD

Changes in lysophospholipids and liver status after weight loss: the RESMENA study

Background: Obesity and comorbidities such as non-alcoholic fatty liver disease (NAFLD) are major public health burdens. Alterations in lipid metabolism are involved in hepatic diseases. The objective of this study was to assess the influence of weight loss on lysophospholipid (LP) metabolism and liver status in obese subjects as well as to provide new evidence regarding the interaction of LP metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage. Methods: Thirty-three subjects from the RESMENA (Reduction of Metabolic Syndrome in Navarra, NCT01087086) study were selected based on their Fatty Liver Index (FLI). Plasma lipid species (lysophosphatidilcholine: LPC, lysophosphatidilethanolamines: LPE and lysophosphatidylinositols: LPI specifically) were determined by LC-MS, while waist circumference (WC) and other non-invasive liver markers such as, FLI and BAAT scores as well as dietary records, anthropometrical measurements, body composition by DXA and other metabolic determinants were analyzed before and after a six-month hypocaloric nutritional intervention. Results: Computed Z-scores of total LP (LPC, LPE, and LPI) were significantly decreased after 6-months of following a hypocaloric diet. Specifically, LPC14:0, LPC15:0, LPC16:1, LPC18:4, LPC20:4, showed clear relationships with weight loss. Changes in FLI score, WC and BAAT score revealed associations with general changes in LPC score. Interestingly the BAAT score was statistically associated with the LPC score after adjustment for weight loss. Conclusion: The lipidomic LPC profile analysis revealed a generalized decrease in circulating lysophospholipids after weight loss. The involvement of particular LP in liver metabolism and obesity merit further attention, as some of these specific non-invasive liver markers were reduced independently of weight loss