Risk Of Developing Nonalcoholic Fatty Liver Disease Research Articles

Depression Exacerbates Hepatic Steatosis in C57BL/6J Mice by Activating the Hypothalamic-Pituitary-Adrenal Axis.

Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known. In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot. The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses. Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them.

Relationship between serum 25-hydroxyvitamine D and non-alcoholic fatty liver disease

Background. Today, non-alcoholic fatty liver disease (NAFLD) is a very common condition that affects ~ 25% of the world’s population. The prevalence of NAFLD is expected to increase further in the coming years due to the obesity pandemic, rising incidence of diabetes and other factors. The search for modifiable risk factors for NAFLD is relevant and urgent to prevent the spread, morbidity and progression of this disease. Recent studies have shown that vitamin D may be a risk factor, which, due to its pleiotropic effects, modulates liver inflammation and fibrogenesis and can improve the liver response to insulin. But there is no definitive opinion on the relationship between vitamin D level and the risk of NAFLD. The purpose of the study was to investigate the serum level of 25(OH)D in patients with NAFLD and to establish its possible relationship with the development and progression of this disease. Materials and methods. A total of 120 patients (78women, 42 men) with a diagnosis of NAFLD aged 18 to 60years were examined. The diagnosis of NAFLD was made based on multimodal ultrasound with steatometry and elastography, increased transaminases in 2 or more measurements, the presence of risk factors such as type 2 diabetes mellitus and/or obesity. Serum 25-hydroxyvitamin D deficiency was considered at its serum level ≥20 and <30ng/ml, and deficiency at<20 ng/ml. Results. The mean level of 25-hydroxyvitamin D (25.7±2.6 ng/ml) in all patients with NAFLD was significantly and reliably lower than in the control group (52.2±6.8 ng/ml, P<0.01), and in people with non-alcoholic steatohepatitis (NASH), it was lower than in those with simple steatosis (24.3±3.0 vs. 27.1±2.2), although the difference was non-significant (P>0.05). In patients with NASH and liver fibrosis, the mean level of 25-hydroxyvitamin D was also lower than in all patients with NAFLD/NASH, especially in severe F3–4 fibrosis, although this difference was also non-significant. Normal vitaminD status was observed in only 42 (35%) patients with NAFLD/NASH, while most people (78 patients, 65%; P<0.005) had a decrease in serum vitamin D levels in the form of its insufficiency or deficiency: 66 (55%) and 12 individuals (10%), respectively. Conclusions. An open-label study found an inverse relationship between 25(OH)D levels and the risk of NAFLD development and progression. Because vitamin D is considered a modifiable risk factor for NAFLD, this finding may be of clinical significance due to the possible preventive effect of vitamin D in this disease.

Interaction between the PNPLA3 Gene and Nutritional Factors on NAFLD Development: The Korean Genome and Epidemiology Study.

Genetic and nutritional factors contribute to the development of non-alcoholic fatty liver disease (NAFLD); however, gene-diet interactions in NAFLD development are poorly understood. In this case-control study, a large dataset from the Korean Genome and Epidemiology Study cohort (n = 72,299) comprising genomic data, medical records, social history, and dietary data was used. We investigated the interactions between the PNPLA3 rs738409 genotype and nutritional factors and their possible effect on the risk of NAFLD development in 2950 patients with NAFLD and 12,907 controls. In the PNPLA3 risk allele group, high protein, fat, sodium, phosphorus, niacin, and vitamin B6 intakes were associated with a decreased risk of NAFLD. In the non-risk allele group, only high fat intake was associated with a decreased risk of NAFLD. Among these nutrients, high sodium intake had a significant protective interaction with the PNPLA3 genotype against NAFLD (p = 0.002). Among salty foods, only kimchi had a significant protective effect against the PNPLA3 genotype (p = 0.012). Thus, the PNPLA3 genotype is differentially associated with nutritional factors. In particular, it interacts with kimchi, a fermented vegetable dish. Therefore, fermented vegetables may serve as a tailored therapeutic food for people with the PNPLA3 risk allele.

Nutrition and physical activity in Asian Indians with non-alcoholic fatty liver: A case control study

AimWe tested the hypothesis that Asian Indians with non-alcoholic fatty liver disease (NAFLD) would have imbalanced diets and lower intensity of physical activity than those without NAFLD. MethodsWe studied dietary intake, intensity of physical activity and anthropometric and metabolic profiles in subjects with NAFLD and in healthy controls. Complete clinical, biochemical, dietary and physical activity profiles were studied for 169 cases and 173 controls in a prospective manner. Bivariate and multivariate analyses were carried out to identify the predictors of NAFLD [odds ratio (OR) and 95% confidence intervals (95%CI)]. ResultsThe mean dietary intakes of total energy, carbohydrate, protein, total fat, saturated fat and total cholesterol were significantly higher, while intake of monounsaturated fatty acids and polyunsaturated fatty acids was significantly lower in cases as compared to controls (p < 0.01 for all). Further, mean physical activity in a day (expressed as MET.Minutes) and total energy expenditure were significantly lower in cases than in controls (33.3 ± 3.6 vs.36.2 ± 0.5, p = 0.001 and 2707.6 ± 505.6 vs. 2904.3 ± 690.3, p = 0.02, respectively). On multivariate analysis, percentage dietary total fat intake (OR: 13.4; 95% CI: 4.6–39.3, p = 0.001), homeostatis model assessment for insulin resistance (OR: 6.9; 95% CI: 3.2–14.8, p = 0.001) abdominal obesity (OR: 2.7; 95% CI: 1.5–5.0, p = 0.001) and high serum triglycerides (OR: 2.1; 95%CI: 1.2–3.8, p = 0.007) were associated with an increased risk for development of NAFLD. ConclusionDecrease in intake of total dietary fats and improvement of insulin resistance, abdominal obesity and blood triglycerides should be important measures for management of NAFLD in Asian Indians in north India.

Association Between LYPLAL1 rs12137855 Polymorphism With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease in a Chinese Han Population.

Background:Recent genome-wide association studies (GWAS) identified that gene Lysophospholipase-like 1 (LYPLAL1) rs12137855 associated with non-alcoholic fatty liver disease (NAFLD). No research has been performed regarding the association between LYPLAL1 and NAFLD in China.Objectives:The aim of the present study was to investigate the association between the gene LYPLAL1 rs12137855 and NAFLD, and the effect on serum lipid profiles in a Chinese Han population.Patients and Methods:LYPLAL1 rs12137855 gene was genotyped in 184 patients with NAFLD and 114 healthy controls using sequencing and polymerase chain reaction analysis (PCR). We tested serum lipid profiles using biochemical methods.Results:No significant differences in genotype and allele frequencies of LYPLAL1 rs12137855 was found between the NAFLD group and the controls group (P > 0.05). Subjects with the variant LYPLAL1 rs12137855 CC genotype had a higher mean weight, body mass index (BMI) and low density lipoprotein (LDL).Conclusions:Our results showed for the first time that LYPLAL1 gene is not associated with a risk of NAFLD development in the Chinese Han population. The variant carriers of overall subjects significantly increased weight, BMI and LDL.

Abstract 20174: Impact of Entrance Examination on Development of Nonalcoholic Fatty Liver Disease in New University Students

Introduction: Nonalcoholic fatty liver disease (NAFLD) has emerged as a risk factor for cardiovascular diseases. In Japan, most of high-school graduates who fail to pass the university entrance examinations attend full-time cram schools to devote themselves to preparing for the examinations for another year(s). These full-time cram-school students, called as “Ronin samurais” in Japanese, could be at risk for development of NAFLD because they live sedentary lifestyle under persistent academic stress. Hypothesis: We assessed the hypothesis that the Ronin-samurai period before entering university is associated with NAFLD in new university students. Methods: This cross-sectional study included 1777 new university students who underwent a group medical check-up immediately after admission into Kanazawa University. Results: Of the 1777 students, 319 (18%) went through the Ronin-samurai period before entering university (Ronin-samurai group). The Ronin-samurai group showed significantly higher body mas index, total cholesterol levels, and alanine aminotransferase (ALT) values compared to the non-Ronin group (n = 1458). The estimated mean difference (B) in ALT values between the two groups was 5.6 ± 1.2 IU/L (P &lt;0.0001). The association persisted even after adjusting for age, gender and metabolic risk factors (B = 3.7 ± 1.5, P = 0.014). The follow-up analysis in 94 students with elevated ALT values (≥ 40 IU/L) after medical check-up showed a drastic decrease in mean ALT values in both groups only 9 weeks after entering the university (Figure), although no lifestyle intervention was performed during the time period. Conclusions: Spending an extra year(s) preparing for the entrance examination, as Ronin samurais, could contribute to this previously unrecognized “entrance examination-related NAFLD” in new university students.

Apolipoprotein c3 gene polymorphisms are not a risk factor for developing non-alcoholic Fatty liver disease: a meta-analysis.

Context:Our objective was to evaluate the effect of gene polymorphisms of apolipoprotein C3 (APOC3) on the development of non-alcoholic fatty liver disease (NAFLD) in different populations.Evidence Acquisition:We performed a meta-analysis of all relevant studies published in the literature. A total of 115 clinical trials or reports were identified, but only seven trials met our inclusion criteria. A meta-analysis was performed according to the Cochrane Reviewers’ Handbook recommendations.Results:Five hospital-based and two population-based case-control studies were included in the final analysis. The overall frequency of APOC3 gene polymorphisms was 67.5% (1177/1745) in NAFLD and 68.8% (988/1437) in controls. The summary odds ratio for the association of gene polymorphisms of APOC3 and the risk of NAFLD was 1.03 (95% CI: 0.89-1.22),which was not statistically significant (P > 0.05).Conclusions:Our meta-analysis, while not ruling out possible publication bias, showed no association between gene polymorphisms of APOC3 and the risk of NAFLD development in different populations in the world.

Evaluation of clinical and inflammatory markers of nonalcoholic fatty liver disease in postmenopausal women with metabolic syndrome.

The aim of this study was to assess clinical and inflammatory markers in nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with metabolic syndrome. This cross-sectional study included 180 Brazilian women (age ≥45 years and amenorrhea ≥12 months). Metabolic syndrome was diagnosed by the presence of at least three of the following indicators: Waist circumference (WC) >88 cm, triglycerides (TGs) ≥150 mg/dL, high-density lipoprotein (HDL) <50 mg/dL; blood pressure ≥130/85 mmHg; and glucose ≥100 mg/dL. NAFLD was diagnosed by abdominal ultrasound. Participants were divided into three groups: Metabolic syndrome alone (n=53); metabolic syndrome+NAFLD (n=67); or absence of metabolic syndrome or NAFLD (control, n=60). Clinical, anthropometric, and biochemical variables were quantified. The inflammatory profile included adiponectin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Data were submitted to statistical analysis using a Tukey test, analysis of variance (ANOVA), chi-squared, Pearson correlation, and logistic regression (odds ratio, OR). Women with metabolic syndrome+NAFLD, abdominal obesity, high glucose, and insulin resistance by HOMA-IR were compared to women with metabolic syndrome alone and controls (P<0.05). High values of IL-6 and TNF-α and low values of adiponectin were observed among women with metabolic syndrome alone or metabolic syndrome+NAFLD when compared to controls (P<0.05). In multivariate analysis, the variables considered as risk of NAFLD development were: High systolic blood pressure (SBP) [(OR 1.02, 95% confidence interval (CI) 1.0-1.04]; large WC (OR 1.07, 95% CI 1.01-1.13); insulin resistance (OR 3.81, 95% CI 2.01-7.13); and metabolic syndrome (OR 8.68, 95% CI 3.3-24.1). Adiponectin levels reduced NAFLD risk (OR 0.88, 95% CI 0.80-0.96). In postmenopausal women, metabolic syndrome, abdominal obesity, and insulin resistance were risk markers for the development of NAFLD, whereas higher adiponectin values indicated a protection marker.

Nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, indeed, worldwide. It has become a global public health issue. In the United States, the prevalence in the general population is estimated at approximately 20%, while that in the morbidly obese population at approximately 75-92% and in the pediatric population at approximately 13-14%. The progressive form of NAFLD, nonalcoholic steatohepatitis, is estimated at approximately 3-5%, with approximately 3-5% of these having progressed to cirrhosis. Thus, the numbers of individuals at risk for end-stage liver disease and development of primary liver cancer is large. NAFLD is an independent risk factor for cardiovascular disease, leads to increased all-cause mortality, and to increased liver-related mortality. This review focuses on recent advances in our understanding of the NAFLD disease spectrum, including etiology, diagnosis, treatment, and genetic and environmental risk factors and suggests future directions for research in this important area.