Assessment of the rs2645424 C/T single nucleotide polymorphisms in the FDFT1 gene, hepatic expression, and serum concentration of the FDFT in patients with nonalcoholic fatty liver disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease worldwide. Considering the powerful association between NAFLD, insulin resistance (IR) and obesity, as well as the key role of ghrelin in these metabolic disorders, we hypothesized that some single nucleotide polymorphisms (SNPs) of the ghrelin (GHRL) and ghrelin receptor (GHSR) genes might be associated with NAFLD. Methods We conducted a case-control retrospective study of 150 cases with biopsy-proven NAFLD and 155 controls. The diagnosis of NAFLD was established before the start of the genotyping process. All the 305 subjects were genotyped for GHRL SNP rs26802 or -501T>G and GHSR SNP rs572169 or Arg159Arg using the PCR-RFLP method. Results The GHRL rs26802 “GG” genotype compared with the “TT” genotype and “TT+TG” genotype appears to be a marker of decreased NAFLD susceptibility even after adjustment for confounding factors (P = 0.006; OR = 0.14, 95% CI = 0.03–0.56 and P = 0.003; OR = 0.16, 95% CI = 0.05–0.53, respectively). However, we observed no significant difference in genotype or allele frequencies between the cases and controls for GHSR SNP rs572169. Conclusions These findings proposed, for the first time, that the GHRL rs26802 “GG” genotype has a protective effect against NAFLD. Nonetheless, this observation warrants further investigations in other populations.

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Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa792 ◽

2020 ◽

Author(s):

Takara L Stanley ◽

Lindsay T Fourman ◽

Isabel Zheng ◽

Colin M McClure ◽

Meghan N Feldpausch ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Binding Proteins ◽

Mrna Levels ◽

Igf Binding Proteins ◽

Nonalcoholic Fatty Liver ◽

Hepatic Expression ◽

Igf Binding

Abstract Context Growth hormone (GH) and IGF-1 help regulate hepatic glucose and lipid metabolism, and reductions in these hormones may contribute to development of nonalcoholic fatty liver disease (NAFLD). Objective To assess relationships between hepatic expression of IGF1 and IGF-binding proteins (IGFBPs) and measures of glycemia and liver disease in adults with NAFLD. Secondarily to assess effects of GH-releasing hormone (GHRH) on circulating IGFBPs. Design Analysis of data from a randomized clinical trial of GHRH. Setting Two US academic medical centers. Participants Participants were 61 men and women 18 to 70 years of age with HIV-infection, ≥5% hepatic fat fraction, including 39 with RNA-Seq data from liver biopsy. Main Outcome Measures Hepatic steatosis, inflammation, and fibrosis by histopathology and measures of glucose homeostasis. Results Hepatic IGF1 mRNA was significantly lower in individuals with higher steatosis and NAFLD Activity Score (NAS) and was inversely related to glucose parameters, independent of circulating IGF-1. Among the IGFBPs, IGFBP2 and IGFBP4 were lower and IGFBP6 and IGFBP7 (also known as IGFBP-related protein 1) were higher with increasing steatosis. Hepatic IGFBP6 and IGFBP7 mRNA levels were positively associated with NAS. IGFBP7 mRNA increased with increasing fibrosis. Hepatic IGFBP1 mRNA was inversely associated with glycemia and insulin resistance, with opposite relationships present for IGFBP3 and IGFBP7. GHRH increased circulating IGFBP-1 and IGFBP-3, but decreased IGFBP-2 and IGFBP-6. Conclusions These data demonstrate novel relationships of IGF-1 and IGFBPs with NAFLD severity and glucose control, with divergent roles seen for different IGFBPs. Moreover, the data provide new information on the complex effects of GHRH on IGFBPs.

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APOC3 rs2070667 Associates with Serum Triglyceride Profile and Hepatic Inflammation in Nonalcoholic Fatty Liver Disease

BioMed Research International ◽

10.1155/2020/8869674 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Qing-Yang Xu ◽

Han Li ◽

Hai-Xia Cao ◽

Qin Pan ◽

Jian-Gao Fan

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Serum Triglyceride ◽

Serum Levels ◽

High Grade ◽

Nucleotide Polymorphisms ◽

Nonalcoholic Fatty Liver ◽

Lobular Inflammation

Single-nucleotide polymorphisms (SNPs) of apolipoprotein C3 (APOC3) play important role in lipid metabolism, and dyslipidemia underlies nonalcoholic fatty liver disease (NAFLD). But the correlation of serum lipidomics, APOC3 SNPs, and NAFLD remains limited understood. Enrolling thirty-four biopsy-proven NAFLD patients from Tianjin, Shanghai, Fujian, we investigated their APOC3 genotype and serum lipid profile by DNA sequencing and ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), respectively. Scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was then performed to reveal the role of lipidomics-affecting APOC3 SNPs in NAFLD-specific pathological alterations. Here, we reported that APOC3 SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) intimately correlated to serum lipidomics in NAFLD patients. A allele instead of G allele at rs2070667, which dominated the SNPs underlying lipidomic alteration, exhibited downregulatory effect on triacylglycerols (TGs: TG 54 : 7, TG 54 : 8, and TG 56 : 9) containing polyunsaturated fatty acid (PUFA). Moreover, subjects with low-level PUFA-containing TGs were predisposed to high-grade lobular inflammation (TG 54 : 7, rho = − 0.454 and P = 0.007 ; TG 54 : 8, rho = − 0.411 and P =0.016; TG 56 : 9, rho = − 0.481 and P = 0.004 ). The significant correlation of APOC3 rs2070667 and inflammation grading [G/G vs. G/A+A/A: 0.00 (0.00 and 1.00) vs. 1.50 (0.75 and 2.00), P = 0.022 ] further confirmed its pathological action on the basis of lipidomics-impacting activity. These findings suggest an inhibitory effect of A allele at APOC3 rs2070667 on serum levels of PUFA-containing TGs, which are associated with high-grade lobular inflammation in NAFLD patients.

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Fish Oil Feeding Modulates the Expression of Hepatic MicroRNAs in a Western-Style Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model

BioMed Research International ◽

10.1155/2017/2503847 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Hualin Wang ◽

Yang Shao ◽

Fahu Yuan ◽

Han Feng ◽

Na Li ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fish Oil ◽

Nonalcoholic Fatty Liver Disease ◽

Rat Model ◽

Fatty Liver Disease ◽

Differentially Expressed ◽

Nonalcoholic Fatty Liver ◽

Hepatic Expression ◽

Fish Oil Supplementation

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases worldwide. Recent studies have indicated that fish oil supplementation has benefits against NAFLD. Our previous transcriptomic study has validated the effect of fish oil supplementation on altering hepatic gene expression in a NAFLD rat model. In the current study, we examined the effects of fish oil on the expression of hepatic microRNAs. Male Sprague–Dawley rats were fed with a lab chow (CON), high-fat high-cholesterol diet (WD), or WD supplemented with fish oil (FOH), respectively. Small RNAs were extracted from livers for RNA-sequencing. A total of 79 miRNAs were identified as differentially expressed miRNAs (DEMs) between FOH and WD groups, exemplified by rno-miR-29c-3p, rno-miR-30d-5p, rno-miR-33-5p, rno-miR-34a, and rno-miR-328a-3p. Functional annotation of DEMs predicted target genes suggested that the altered hepatic miRNAs contributed to fish oil modification of hepatic lipid metabolism and signaling transduction. Integrative analysis of DEMs and differentially expressed genes suggested that the expression difference of Pcsk9, Insig2, Per3, and Socs1/3 between FOH and WD groups may be due to miRNA modification. Our study reveals that fish oil supplementation alters hepatic expression of miRNAs, which may contribute to fish oil amelioration of NAFLD in rats.

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