Dynamics of Serum Retinol and Alpha-Tocopherol Levels According to Non-Alcoholic Fatty Liver Disease Status.
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ABSTRACT:
SUBMITTER: Jeon D
PROVIDER: S-EPMC8161312 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMicronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, β-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers.MethodsBaseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models.ResultsHigher β-carotene and retinol levels were associated with less liver cancer (β-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend=0.0009) and CLD mortality (β-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend=0.77). Participants with higher levels of β-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels.ConclusionsOur findings suggest that higher concentrations of β-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.
| S-EPMC4260018 | biostudies-literature
Project description:Previous reports on the association between retinol binding protein 4 (RBP4) and nonalcoholic fatty liver disease (NAFLD) were controversial. This study aimed to investigate the association between the serum RBP4 levels and occurrence of NAFLD in Chinese population. In total, 2938 participants aged 40-75 years were involved in this community-based cross-sectional study. General information, lifestyle factors, serum levels of RBP4 and the presence of NAFLD were determined. Patients with NAFLD had significantly higher concentrations of RBP4 (37.9?±?6.8??g/ml) than did non-NAFLD controls (35.0?±?6.7??g/ml) (P?<?0.001). The odds ratios (ORs) of NAFLD for the highest (vs. lowest) quartile of RBP4 were 1.884 (95% CI: 1.391, 2.551) for females (P?<?0.001), and 2.107 (95% CI: 1.357, 3.273) for male participants (P?<?0.01) after adjusting for related factors. The serum RBP4 levels were positively associated with the prevalence of NAFLD in middle-aged and elderly Chinese people, and Homeostatic model assessment-insulin resistance (HOMA-IR), trunk fat, the waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) might be implicated in the pathogenesis of RBP4 in NAFLD.
| S-EPMC5362806 | biostudies-literature
Project description:The role of retinol in the prevention of multifactorial chronic diseases remains uncertain, and there is sparse evidence regarding biological actions and pathways implicated in its effects on various outcomes. The aim is to investigate whether serum retinol in an un-supplemented state is associated with low molecular weight circulating metabolites. We performed a metabolomic analysis of 1,282 male smoker participants based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We examined the association between 947 metabolites measured by ultra-high performance LC-MS/GC-MS and retinol concentration (from HPLC) using linear regression that estimated the difference in metabolite concentrations per unit difference in retinol concentration as standardized ?-coefficients and standard errors (SE). We identified 63 metabolites associated with serum retinol below the Bonferroni-corrected P-value (p?<?5.3?×?10-5). The strongest signals were for N-acetyltryptophan (??=?0.27; SE?=?0.032; p?=?9.8?×?10-17), myo-inositol (??=?0.23; SE?=?0.032; p?=?9.8?×?10-13), and 1-palmitoylglycerophosphoethanolamine (??=?0.22; SE?=?0.032; p?=?3.2?×?10-12). Several chemical class pathways were strongly associated with retinol, including amino acids (p?=?1.6?×?10-10), lipids (p?=?3.3?×?10-7), and cofactor/vitamin metabolites (3.3?×?10-7). The strongest sub-pathway association was for inositol metabolism (p?=?2.0?×?10-14). Serum retinol concentration is associated with circulating metabolites in various metabolic pathways, particularly lipids, amino acids, and cofactors/vitamins. These interrelationships may have relevance to the biological actions of retinol, including its role in carcinogenesis.
| S-EPMC5587770 | biostudies-literature
Project description:1. The ability of a number of carboxylic acids, their esters, retinol and alpha-tocopherol to induce fusion of hen erythrocytes in vitro was investigated. 2. Some 30 different fat-soluble substances (100mug/ml) were found to cause the formation of multinucleated erythrocytes with a suspension of 3x10(8) erythrocytes/ml. The most effective agents induced fusion within 5-10min at 37 degrees C; some substances required about 1h. 3. Inclusion of Dextran 60C in the test medium minimized colloid osmotic lysis caused by exogenous lipids that induce cell fusion. 4. Cell swelling, followed by cell adhesion, was then seen to precede cell fusion. 5. Fusion occurred with C(10)-C(14) saturated carboxylic acids, with unsaturated, longer-chain carboxylic acids and their mono-esters; retinol, and to a lesser extent alpha-tocopherol, also caused cell fusion. 6. C(6)-C(9), C(15), C(16) and C(18) saturated carboxylic acids did not induce fusion within 4h; glyceryl dioleate was only weakly active, and glyceryl trioleate was inactive in the test system. 7. Fusion was facilitated by a high ratio of chemical agents to cell number and by incubation between pH5 and 6. It was inhibited by EDTA and by serum albumin. 8. Glyceryl mono-oleate caused both a similar fusion of several species of mammalian erythrocyte and the interspecific fusion of human and chicken erythrocytes. 9. The term ;fusogenic' is proposed to describe chemical, viral and physical agents that cause membranes to fuse. 10. The biochemical mechanisms involved and the possible biological significance of membrane fusion by fusogenic lipids are discussed.
| S-EPMC1165934 | biostudies-other
Project description:Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) is a chronic liver disease commonly associated with hepatic fibrosis. NASH patients have an increased risk for hepatocellular carcinoma (HCC). An altered retinol metabolism is one of the pathways involved in the process of hepatic fibrosis, and enzymes involved in retinol metabolism have been associated with HCC. We aimed to determine the association between plasma retinol levels and hepatic expression of genes related to retinol metabolism, as well as to assess the hepatic expression of transcription factors regulated by retinoic acid in patients with NAFLD. Cross-sectional study where hepatic gene expression (Illumina microarray) and plasma retinol levels (HPLC) were measured in 17 patients with simple steatosis (SS), 15 with NASH, and 22 living liver donors (LD) as controls. Plasma retinol levels were higher in SS (1.53 ± 0.44 ?mol/L) and NASH (1.51 ± 0.56 ?mol/L) compared to LD (1.21 ± 0.38 ?mol/L; p<0.05). AKR1B10 was highly overexpressed in NASH compared to SS (+6.2-fold) and LD (+9.9-fold; p = 4.89E-11). Retinaldehyde dehydrogenase 1 family, member A2 (ALDH1A2) and retinaldehyde dehydrogenase 1 family, member A3 (ALDH1A3), key enzymes for retinoic acid synthesis, were underexpressed in SS (-1.48 and -2.3-fold, respectively) and NASH (-1.47 and -2.6-fold, respectively) versus LD. In NASH, hepatic ALDH1A2 and ALDH1A3 were underexpressed and inversely correlated with plasma retinol levels, which may reduce retinoic acid in the liver. This, in addition to changes in expression of other genes involved in retinol metabolism, suggests a role for altered retinol homeostasis in NASH.
| S-EPMC6209208 | biostudies-literature
Project description:Irisin is a recently found myokine that aids obesity control and improves glucose homeostasis by acting on white adipose tissue cells and increases total energy consumption. The aim of this study was to evaluate serum irisin levels in patients with non-alcoholic fatty liver disease (NAFLD) and to compare these levels with those of normal controls. Among 595 health screen examinees who had visited our institute between January 2013 to March 2013, 355 patients (84 NAFLD patients and 271 normal controls) were enrolled depending on whether they gave written informed consents and their history of alcohol intake, blood tests, and abdominal ultrasonographic findings. Age; sex; laboratory test parameters; homeostasis model assessment-insulin resistance; and levels of leptin, adiponectin, and irisin were assessed. Serum irisin levels (ng/ml) were significantly higher in the NAFLD group than in normal controls (63.4 ± 32.6 vs. 43.0 ± 29.7, p<0.001) and higher in the mild fatty liver group than in the moderate-to-severe fatty liver group (68.3 ± 38.2 vs. 56.6 ± 21.2, p<0.001). Additionally, serum irisin levels were not different between the non-obese and obese groups (48.4 ± 34.2 vs. 45.8 ± 22.9, p = 0.492); however, the levels were significantly lowest in normal controls and highest in the mild fatty liver group in the non-obese (44.9 ± 31.7 vs. 73.1 ± 48.5 vs 59.7 ± 18.0, p<0.001) and obese groups (35.0 ± 17.0 vs. 62.9 ± 21.2 vs. 54.6 ± 23.3, p<0.001). Serum irisin levels were significantly higher in NAFLD patients, which is not consistent with the results of previously published studies. Therefore, more studies are needed to confirm the role of irisin in NAFLD.
| S-EPMC4208808 | biostudies-literature
Project description:BackgroundsTo investigate the value of prolactin (PRL) in diagnosing non-alcoholic fatty liver disease (NAFLD).MethodsMetabolic parameters and serum PRL levels were measured in 452 males and 421 females, who were randomized to the estimation or the validation group as a 1:1 ratio. Hepatic steatosis was diagnosed via abdominal ultrasound. Variables that significantly associated with NAFLD in univariate analysis were included in multiple logistic regression. We used the receiver operator characteristic (ROC) curves to test the model performance. Besides, 147 patients underwent metabolic and liver biopsy were analyzed to validate the diagnostic value of this model.ResultsBody mass index, alanine aminotransferase, prolactin, high density lipoprotein cholesterol and HbA1c were included into models. In males, the area under ROC curve (AUC) was 0.86 (95%CI: 0.82-0.91) for the validation group. With two cut-off points (- 0.79 and 1.71), the sensitivity and specificity for predicting NALFD was 95.2 and 91.1% in the validation group, respectively. In females, the AUC was 0.82 (95%CI: 0.76-0.88) for the validation group. With two cut-off points (- 0.68 and 2.16), the sensitivity and specificity for predicting NALFD was 97.1 and 91.4% in the validation group, respectively. In subjects with liver pathology, the AUC was higher than that of fatty liver index. A positive correlation between the scores of the model and the severities of NAFLD was observed. Importantly, we demonstrated a potential value of this model in predicting nonalcoholic steatohepatitis.ConclusionWe established a mathematic model that can conveniently and effectively diagnose the existence and severities of NAFLD.
| S-EPMC6882057 | biostudies-literature
Project description:PURPOSE: Altered redox status has been implicated in pathogenesis of alcoholic liver disease (ALD) as well as in nonalcoholic fatty liver disease (NAFLD). This study was planned to find the relative role of redox status in these two diseases. METHODS: A total of 44 patients with ALD and 32 patients with NAFLD and 25 apparently healthy controls were included in the study. Redox status was estimated by measuring oxidative stress (superoxide dismutase (SOD) and lipid peroxidation products as thiobarbituric acid reactive substances (TBARS)) and antioxidant status (ferric reducing ability of plasma (FRAP) and vitamin C). RESULTS: TBARS level was raised significantly in both ALD (3.5 (2.3-9.4) vs. 1.8 (0.5-4.1) nmol/ml; P = 0.0001) and NAFLD (5.1 (1-10.2) vs. 1.82 (0.51-4.1) nmol/ml; P = 0.0001) as compared with controls, but was not different between ALD and NAFLD. SOD was significantly higher in ALD as compared to NAFLD (2.4 (1.3-7.8) vs. 0.68 (0.05-19.1) U/ml; P = 0.0001) and controls (1.12 (0.01-3.5) U/ml; P = 0.001). FRAP was lower in ALD as compared with NAFLD (345.4 (56-615.9) vs. 434.1 (197.6-733.3) mumol of Fe(+2) liberated; P = 0.001) but similar to that of controls (340.9 (141.5-697.5) mumol of Fe(+2) liberated). CONCLUSIONS: ALD patients have a higher degree of redox imbalance as compared with NAFLD patients.
| S-EPMC2716853 | biostudies-other
Project description:BACKGROUND: Serum bilirubin may have potent antioxidant and cytoprotective effects. Serum bilirubin levels are inversely associated with several cardiovascular and metabolic endpoints, but their association with nonalcoholic fatty liver disease (NAFLD) has not been investigated except for a single cross-sectional study in a pediatric population. We assessed the prospective association between serum bilirubin concentrations (total, direct, and indirect) and the risk for NAFLD. METHODS AND FINDINGS: We performed a cohort study in 5,900 Korean men, 30 to 59 years of age, with no evidence of liver disease and no major risk factors for liver disease at baseline. Study participants were followed in annual or biennial health examinations between 2002 and 2009. The presence of fatty liver was determined at each visit by ultrasonography. We observed 1,938 incident cases of NAFLD during 28,101.8 person-years of follow-up. Increasing levels of serum direct bilirubin were progressively associated with a decreasing incidence of NAFLD. In age-adjusted models, the hazard ratio for NAFLD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.61 (95% CI 0.54-0.68). The association persisted after adjusting for multiple metabolic parameters (hazard ratio comparing the highest to the lowest quartile 0.86, 95% CI 0.76-0.98; P trend?=?0.039). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of NAFLD. CONCLUSIONS: In this large prospective study, higher serum direct bilirubin levels were significantly associated with a lower risk of developing NAFLD, even adjusting for a variety of metabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for NAFLD risk.
| S-EPMC3352875 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) based on the existence of ballooned hepatocytes, although the states have been known to transform into each other. Moreover, since the detection of ballooned hepatocytes may be difficult with limited biopsied specimens, its clinical significance needs reconsideration. Repeated liver biopsy to assess histological NAFLD activity for therapeutic response is also impractical, creating the need for body fluid biomarkers and less invasive imaging modalities. Recent longitudinal observational studies have emphasized the importance of advanced fibrosis as a determinant of NAFLD outcome. Thus, identifying predictors of fibrosis progression and developing better screening methods will enable clinicians to isolate high-risk NAFLD patients requiring early intensive intervention. Despite the considerable heterogeneity of NAFLD with regard to underlying disease, patient age, and fibrosis stage, several clinical trials are underway to develop a first-in-class drug. In this review, we summarize the present status and future direction of NAFLD/NASH research towards solving unmet medical needs.
| S-EPMC6337019 | biostudies-literature