Natural Extracts Abolished Lipid Accumulation in Cells Harbouring non-favourable PNPLA3 genotype.

Background & aims. G-allele of PNPLA3 (rs738409) favours triglycerides accumulation and steatosis. In this study, we examined the effect of quercetin and natural extracts from mushroom and artichoke on reducing lipid accumulation in hepatic cells. MATERIAL AND METHODS: Huh7.5 cells were exposed to oleic acid (OA) and treated with quercetin and extracts to observe the lipid accumulation, the intracellular-TG concentration and the LD size. Sterol regulatory element binding proteins-1 (SREBP-1), peroxisome proliferator-activated receptor (PPARα-γ) and cholesterol acyltransferase (ACAT) gene expression levels were analysed. RESULTS: Quercetin decreased the intracellular lipids, LD size and the levels of intracellular-TG through the down-regulation of SREBP-1c, PPARγ and ACAT1 increasing PPARα. The natural-extracts suppressed OA-induced lipid accumulation and the intracellular-TG. They down-regulate the hepatic lipogenesis through SREBP-1c, besides the activation of lipolysis through the increasing of PPARα expression. CONCLUSIONS: Quercetin and the aqueous extracts decrease intracellular lipid accumulation by down-regulation of lipogenesis and up-regulation of lipolysis.

Hypovitaminosis D and its relation to demographic and laboratory data among hepatitis C patients.

BACKGROUND: The relationship between 25-hydroxyvitamin D [25(OH)D] serum levels and response to antiviral therapy and laboratory data in HCV infection remains unclear. The aim of this study was to determine pre-treatment 25(OH)D serum level among HCV infected individuals and to evaluate the association between vitamin D status, virological response, and laboratory data. MATERIAL AND METHODS: Baseline serum 25(OH)D levels were measured in 237 chronic HCV infected patients (139 female, age 53.7 ± 11.2 years) using chemiluminescence immunoassay. Correlations between serum 25(OH)D levels, virological and laboratory data regarding HCV infection as well as sustained virological response (SVR) to antiviral therapy were evaluated. RESULTS: Mean serum values of 25(OH)D was 26.2 ± 12 ng/mL and prevalence of vitamin D deficiency (< 30 ng/mL) was 66.2%. Advanced age (> 55 years), high mean values of LDL, total cholesterol, HDL and low mean values of alkaline phosphatase and hemoglobin were statistically associated to vitamin D deficiency. Antiviral treatment was underwent by 133 HCV patients and 44.3% of them achieved SVR. Most of individuals that presented SVR also presented 25(OH)D level higher than 30ng/mL (55.9%). SVR was associated to low mean values of LDL, total cholesterol and platelets; high mean values of ALT, AST and low fibrosis grade. CONCLUSIONS: In conclusion, low vitamin D levels were observed among HCV infected patients and was associated to laboratory findings, however baseline 25(OH)D level is not independently associated with SVR.

PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) is associated with a higher prevalence of steatosis compared to the general population. AIM: Our aim was to assess the impact of PNPLA3 rs738409 G-allele on steatosis in HCV patients. MATERIAL AND METHODS: We included 474 HCV patients treated with peginterferon plus ribavirin. PNPLA3 rs738409 was genotyped and patients were classified according to alleles and genotypes. Steatosis was detected in 46.4% (220/474). Fibrosis was assessed by Scheuer score. Gene expression was analyzed in Huh7.5 and Huh7 cells using Real Time-PCR. RESULTS: PNPLA3 allele-G was associated with steatosis [54.1% (126/233) vs. 39% (94/241)] (p = 0.0001). In HCV-1, allele-G was related to steatosis [50.6% (82/162) vs. 32.3% (53/164)] (p = 0.001), but did not in HCV-3 [61.9% (26/42) vs. 62% (31/50)] (p = 0.993). PNPLA3 allele-G was associated with steatosis in patients with IL28B-CT/TT [57.7% (82/142) vs. 37.1% (56/151)] (p = 0.0001), but did not in IL28B-CC [47.8% (43/90) vs. 42% (37/88)] (p = 0.442). Independent variables associated with steatosis were: PNPLA3 G-allele [O.R. 1.84 (CI95%: 1.06-3.21); p = 0.007], age [O.R. 1.04 (CI95%: 1.01-1.07); p = 0.017], HCV-genotype 3 [O.R. 2.46 (CI95%: 1.30-4.65); p = 0.006], HOMA > 4 [O.R. 2.72 (CI95%: 1.27-5.82); p = 0.010]. Since PNPLA3 RNA could not be detected on PBMC from HCV patients, an in vitro analysis was performed. Huh7.5 cells infected with JFH1 had a decreased PNPLA3 gene expression (fold inhibition = 3.2 ± 0.2), while Huh7 cells presented increased PNPLA3 gene expression (fold induction = 1.5 ± 0.2). CONCLUSION: PNPLA3 allele-G modulated the development of steatosis, particularly in patients with HCV-1 and IL28B-CT/TT genotype, but was not associated with SVR. Metabolic but not viral steatosis seems to be PNPLA3 regulated. Gene interaction may result in differential PNPLA3 gene expression levels in HCV infection.