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OBJECTIVE: To explore the role of tagging single nucleotide polymorphisms (tagSNPs) in the adiponectin gene in the natural course of nonalcoholic fatty liver disease (NAFLD). METHODS: The participants were chosen from our previous survey containing 3543 individuals. Finally, a total of 696 participants who had been followed up for a median of 4 years were included. Each participant was administered with an interview, physical examination, blood tests and ultrasonic examination at both baseline and end-point. Polymerase chain reaction-restriction fragment length polymorphism was applied to determine seven tagSNPs in the adiponectin gene, namely, rs182052, rs16861205, rs822396, rs7627128, rs1501299, rs2241767 and rs3774261. Ordinal logistic regression was used to screen risk factors of NAFLD progression as well as the susceptibility to the disease. Haplotypes analyses were performed to confirm the results. RESULTS: After adjusting for age and gender, rs1501299 (G276T), rs2241767 (A45G) and rs3774261 (A712G) were found to be risk factors of both susceptibility (OR 5.040, 7.471 and 3.546, respectively) and progression (OR 3.83, 3.51 and 3.30, respectively) to NAFLD. Nevertheless, rs182052, rs16861205, rs822396 and rs7627128 had no impact on them. These findings were confirmed by haplotype analysis. CONCLUSION: The tagSNPs rs2241767, rs1501299 and rs3774261 in the adiponectin gene are risk factors for the individuals' susceptibility to and progression of NAFLD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, the natural course of which has not been well documented. This study aimed to perform a prospective cohort study to investigate NAFLD in a Chinese population. METHODS: Using our previous epidemiological survey, 3543 patients were followed-up for a median of 4 years (range 3.6-4.8 years). Of these patients, 624 participated in a new survey. Interviews, physical examinations, biochemical tests and abdominal ultrasonography were repeated for these patient. RESULTS: The annual incidence of NAFLD was 9.1% (male 7.3% vs female 9.7%, P = 0.047). Among 117 NAFLD patients at baseline, 51 (43.6%) remained unchanged, 26 (22.2%) became worse, and 40 (34.2%) improved. Patients with simultaneous metabolic syndrome (MS) showed accelerated progression ( P = 0.026). For the NAFLD patients, both general annual mortality rates and cardiovascular disease deaths (both 0.54%) were significantly higher than those of patients without NAFLD (0.19% and 0.17%, P = 0.005). Age and several variables related to MS were risk factors for NAFLD progression. CONCLUSIONS: The incidence of NAFLD in southern China is relatively lower in comparison with that of the developed countries. Patients with NAFLD have a benign prognosis. Variables related to MS are risk factors for NAFLD occurrence and progression. [ABSTRACT FROM AUTHOR]

Background/Aims: Peroxisome proliferator-activated receptors-γ (PPAR-γ) and its co-activator-1α (PGC-1α) are involved in the regulation of lipid and glucose metabolisms. This study aimed to investigate the genetic polymorphisms of PPAR-γ and PGC-1α in Chinese people and their influence on plasma adiponectin levels and non-alcoholic fatty liver disease (NAFLD) susceptibility. Methods: Ninety-six patients with NAFLD and 96 healthy controls were included. The single nucleotide polymorphisms (SNPs) of C161T PPAR-γand Gly482Ser PGC-1α genes were analysed by polymerase chain reaction and restriction fragment length polymorphism. Result: The CC, CT and TT genotypic distributions of the NAFLD group were significantly different from those of controls (55.2, 39.6, 5.2 vs. 74.0, 25.0, 1.0%; P=0.015). The allelic frequencies of C and T were also different between the two groups ( P=0.004). As for the PGC-1α gene, there was no difference of the genotypic and allelic frequencies between the two groups ( P>0.05). In NAFLD patients, the plasma adiponectin concentrations were lower in the PPAR-γ CT/TT genotypes compared with those in the CC genotype group (3.0±0.6 vs. 4.3±0.9, P=0.02). Multivariate logistic regression analysis showed that CT/TT genotypes of PPAR-γ, TG, waist hip ratio, hypoadiponectinaemia and homoeostasis model assessment (HOMA)-IR were the risk factors for NAFLD. Conclusion: SNPs in the PPAR-γ, but not PGC-1α, gene are associated with NAFLD susceptibility possibly through the adiponectin pathway. [ABSTRACT FROM AUTHOR]

Background and Purpose: Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Astaxanthin (Ax) is a carotenoid, and beneficial effects of astaxanthin, including anti-oxidative, anti-inflammatory, and anti-tumour activity, have been identified. The present study aimed to elucidate the protective effect of astaxanthin against NAFLD and its underlying mechanism.Experimental Approach: Mice were fed either a high fat or chow diet, with or without astaxanthin, for up to 12 weeks. L02 cells were treated with free fatty acids combined with different doses of astaxanthin for 48 h. Histopathology, expression of lipid metabolism, inflammation, apoptosis, and fibrosis-related gene expression were assessed. And the function of mitochondria was also evaluated.Key Results: The results indicated that astaxanthin attenuated HFD- and FFA-induced lipid accumulation and its associated oxidative stress, cell apoptosis, inflammation, and fibrosis both in vivo and in vitro. Astaxanthin up-regulated FGF21 and PGC-1α expression in damaged hepatocytes, which suggested an unrecognized mechanism of astaxanthin on ameliorating NAFLD.Conclusion and Implications: Astaxanthin attenuated hepatocyte damage and mitochondrial dysfunction in NAFLD by up-regulating FGF21/PGC-1α pathway. Our results suggest that astaxanthin may become a promising drug to treat or relieve NAFLD. [ABSTRACT FROM AUTHOR]

The article reports that alcoholic liver disease (ALD), induced by long-term heavy alcohol consumption, encompasses a progressive clinical-histological spectrum of liver injuries from simple fatty liver to alcoholic hepatitis, hepatic fibrosis and cirrhosis. It notes that hepatitis virus infection exerts a synergistic effect on alcohol-induced liver injury. It adds that ALD could both accelerate the development and progression of liver diseases.

The article reports that non-alcoholic fatty liver disease (NAFLD) is an acquired metabolic stress-induced liver disease associated closely with genetic susceptibility and insulin resistance. It notes that major risk factors for NAFLD include obesity-related high-calorie dietary rich in saturated fat and fructose, and sedentary lifestyles. It adds that increased waist circumference and IR have a strong correlation with NAFLD than increased subcutaneous fat deposit and high body mass index.

Objective To investigate the role of adiponectin precursor ( ADIPOQ) DNA methylation in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the effect of curcumin on the development of NAFLD using rat models. Methods Male Sprague-Dawley rats were divided into the control, NAFLD and curcumin-treated groups. The genetic and epigenetic features of each rat were measured and recorded. Real-time polymerase chain reaction (PCR), Western blot and bisulfite sequencing PCR (BSP) were used to quantify the ADIPOQ mRNA and protein expressions, and DNA methylation status, respectively. Results Serum levels of alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and fasting blood glucose in the NAFLD group were significantly increased compared with the control group. The genetic and epigenetic features were reversed after curcumin treatment. The ADIPOQ mRNA and protein expressions in the livers of the NAFLD rats was lower compared with the control and the curcumin-treated groups. ADIPOQ methylation rate in the NAFLD group was significantly higher than in the control group, which was declined slightly following curcumin treatment. A negative correlation was found between the degrees of DNA methylation and ADIPOQ mRNA expression. ALT, TC, TG and homeostatic model assessment insulin resistance index had a positive correlation with ADIPOQ DNA methylation , showing that curcumin might affect the gene expression involved in lipid and glucose metabolism by influencing ADIPOQ DNA methylation modifications, which contributed to alleviation of NAFLD. Conclusion Altering the DNA methylation of ADIPOQ is one of the mechanisms by which curcumin executes its hepatoprotective function in NAFLD. [ABSTRACT FROM AUTHOR]

Background & Aims Controlled attenuation parameter ( CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance ( SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement ( LSM). Methods Of 101 patients with non-alcoholic fatty liver disease ( NAFLD) and 280 patients with chronic hepatitis B ( CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves ( AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. Results SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. Conclusion CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients. [ABSTRACT FROM AUTHOR]