Search Results (11)

Background/Objectives: This study investigates the gut microbiota’s role in metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on microbial and functional signatures and sex-based differences. Methods: Using baseline data from 98 MASLD patients and 45 controls from the Fatty Liver in Obesity (FLiO) study, the gut microbiota was profiled with 16S gene sequencing, followed by statistical and machine learning analyses to identify disease-associated microbial signatures. Results: Notable alpha and beta diversity differences were observed between MASLD patients and the controls, varying by sex. Machine learning models highlighted specific microbial signatures for each sex, achieving high accuracy (area under the receiver operating characteristic curves of 0.91 for women and 0.72 for men). The key microbial taxa linked to MASLD included Christensenella and Limosilactobacillus in women and Beduinibacterium and Anaerotruncus in men. Functional profiling showed that MASLD patients had increased pathways for amine biosynthesis and amino acid degradation, while the controls exhibited enhanced fermentation pathways. These microbial features were associated with systemic inflammation, insulin resistance, and metabolite production linked to gut dysbiosis. Conclusions: The findings support the potential of gut microbiota signatures to be used as non-invasive indicators of MASLD and highlight sex-specific variations that could inform personalized diagnostic and therapeutic approaches. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), with a prevalence of 30% of adults globally, is considered a multifactorial disease. There is a lack of effective non-invasive methods for accurate diagnosis and monitoring. Therefore, this study aimed to explore associations between changes in circulating miRNA levels, inflammatory markers, and depressive symptoms with hepatic variables in MASLD subjects and their combined potential to predict the disease after following a dietary intervention. Biochemical markers, body composition, circulating miRNAs and hepatic and psychological status of 55 subjects with MASLD with obesity and overweight from the FLiO study were evaluated by undergoing a 6-, 12- and 24-month nutritional intervention. The highest accuracy values of combined panels to predict the disease were identified after 24 months. A combination panel that included changes in liver stiffness, high-density lipoprotein cholesterol (HDL-c), body mass index (BMI), depressive symptoms, and triglycerides (TG) yielded an AUC of 0.90. Another panel that included changes in hepatic fat content, total cholesterol (TC), miR15b-3p, TG, and depressive symptoms revealed an AUC of 0.89. These findings identify non-invasive biomarker panels including circulating miRNAs, inflammatory markers, depressive symptoms and other metabolic variables for predicting MASLD presence and emphasize the importance of precision nutrition in MASLD management and the sustained adherence to healthy lifestyle patterns. Full article

The purpose of this study was to investigate the possibility of implementing an artificial intelligence (AI) approach for the analysis of fluorescence lifetime imaging ophthalmoscopy (FLIO) data even with small data. FLIO data, including the fluorescence intensity and mean fluorescence lifetime (τm) of two spectral channels, as well as OCT-A data from 26 non-smokers and 28 smokers without systemic and ocular diseases were used. The analysis was performed with support vector machines (SVMs), a well-known AI method for small datasets, and compared with the results of convolutional neural networks (CNNs) and autoencoder networks. The SVM was the only tested AI method, which was able to distinguish τ_m between non-smokers and heavy smokers. The accuracy was about 80%. OCT-A data did not show significant differences. The feasibility and usefulness of the AI in analyzing FLIO and OCT-A data without any apparent retinal diseases were demonstrated. Although further studies with larger datasets are necessary to validate the results, the results greatly suggest that AI could be useful in analyzing FLIO-data even from healthy subjects without retinal disease and even with small datasets. AI-assisted FLIO is expected to greatly advance early retinal diagnosis. Full article

Deposition of calcium-containing minerals such as hydroxyapatite and whitlockite in the subretinal pigment epithelial (sub-RPE) space of the retina is linked to the development of and progression to the end-stage of age-related macular degeneration (AMD). AMD is the most common eye disease causing blindness amongst the elderly in developed countries; early diagnosis is desirable, particularly to begin treatment where available. Calcification in the sub-RPE space is also directly linked to other diseases such as Pseudoxanthoma elasticum (PXE). We found that these mineral deposits could be imaged by fluorescence using tetracycline antibiotics as specific stains. Binding of tetracyclines to the minerals was accompanied by increases in fluorescence intensity and fluorescence lifetime. The lifetimes for tetracyclines differed substantially from the known background lifetime of the existing natural retinal fluorophores, suggesting that calcification could be visualized by lifetime imaging. However, the excitation wavelengths used to excite these lifetime changes were generally shorter than those approved for retinal imaging. Here, we show that tetracycline-stained drusen in post mortem human retinas may be imaged by fluorescence lifetime contrast using multiphoton (infrared) excitation. For this pilot study, ten eyes from six anonymous deceased donors (3 female, 3 male, mean age 83.7 years, range 79–97 years) were obtained with informed consent from the Maryland State Anatomy Board with ethical oversight and approval by the Institutional Review Board. Full article

Neck circumference (NC) and its relationship to height (NHtR) and weight (NWtR) appear to be good candidates for the non-invasive management of non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the ability of routine variables to assess and manage NAFLD in 98 obese subjects with NAFLD included in a 2-year nutritional intervention program. Different measurements were performed at baseline, 6, 12 and 24 months. The nutritional intervention significantly improved the anthropometric, metabolic and imaging variables. NC was significantly associated with the steatosis degree at baseline (r = 0.29), 6 m (r = 0.22), 12 m (r = 0.25), and 24 m (r = 0.39) (all p < 0.05). NC was also significantly associated with visceral adipose tissue at all the study time-points (basal r = 0.78; 6 m r = 0.65; 12 m r = 0.71; 24 m r = 0.77; all p < 0.05). NC and neck ratios combined with ALT levels and HOMA-IR showed a good prediction ability for hepatic fat content and hepatic steatosis (at all time-points) in a ROC analysis. The model improved when weight loss was included in the panel (NC-ROC: 0.982 for steatosis degree). NC and ratios combined with ALT and HOMA-IR showed a good prediction ability for hepatic fat during the intervention. Thus, their application in clinical practice could improve the prevention and management of NAFLD. Full article

Fluorescence lifetime imaging microscopy (FLIM) evaluates the metabolic state of tissue based on reduced nicotinamide adenine dinucleotide (NAD(P)H) and flavin adenine dinucleotide (FAD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) can image the fundus of the eyes, but cannot detect NAD(P)H. We used multiphoton FLIM to study the metabolic state of the retina in fixed eyes of wild-type mice C57BL6/J. We sectioned the eye using a polyacrylamide gel-embedding technique and estimated the percentage of bound NAD(P)H. We found that oxidative phosphorylation was the predominant metabolic state, particularly in the inner retina, when a fixed retina was used. We also demonstrated the feasibility of FAD imaging of the retina. In addition, we demonstrated that autofluorescence and various FLIM channels, such as hemoglobin, melanin and collagen, can be used to evaluate the structure of the retina and other parts of the eye without any special staining. Full article

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) (GRS_FLI), lipidomic-OWLiver^®-test (GRS_OWL) and magnetic resonance imaging (MRI) (GRS_MRI), 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 GRS_FLI, GRS_OWL and GRS_MRI 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. Full article

Fluorescence Lifetime (FLT) of intrinsic fluorophores may alter under the change in metabolic state. In this study, the FLT of rabbit retina was investigated in vivo after laser irradiation using fluorescence lifetime imaging ophthalmoscopy (FLIO). The retina of the Chinchilla bastard rabbits was irradiated with a 514 nm diode laser. FLIO, fundus photography, and optical coherence tomography (OCT) were conducted 30 min and 1 to 3 weeks after treatment. After strong coagulation, the FLT at laser spots was significantly elongated immediately after irradiation, conversely shortened after more than a week. Histological examination showed eosinophilic substance and melanin clumping in subretinal space at the coagulation spots older than one week. The FLT was also elongated right around the coagulation spots, which corresponded to the discontinuous ellipsoid zone (EZ) on OCT. This EZ change was recovered after one week, and the FLT became the same level as the surroundings. In addition, there was a region around the laser spot where the FLT was temporarily shorter than the surrounding area. When weak pulse energy was applied to selectively destroy only the RPE, a shortening of the FLT was observed immediately around the laser spot within one week after irradiation. FLIO could serve as a tool to evaluate the structural and metabolic response of the retina to laser treatments. Full article

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). Full article

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. Full article

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. Full article