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Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease.

ABSTRACT: BACKGROUND & AIMS:Dietary modification has been recommended for treatment of nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent its development. We performed a prospective study to examine the association between diet quality change and change in liver fat. We also examined the association between genetic risk score and liver fat change in individuals with different levels of diet quality change. METHODS:Our study included 1521 participants who attended the seventh and eighth examinations (1998-2001 and 2005-2008) of the second-generation cohort or attended the first and second examinations (2002-2005 and 2008-2011) of the third-generation cohort in the Framingham Heart Study. The self-administered semiquantitative 126-item Harvard food frequency questionnaire was used to determine dietary intake in the year leading up to an examination. We assessed levels of liver fat using liver-phantom ratio (LPR) on computed tomography images from 2002 through 2005 and again from 2008 through 2011. LPR values are inversely related to liver fat: increased LPR indicates decreased liver fat. We examined associations of changes in 2 diet scores, the Mediterranean-style diet score (MDS) and Alternative Healthy Eating Index (AHEI), with changes in liver fat and new-onset fatty liver. We evaluated interactions between diet score change and a weighted genetic risk score for NAFLD, determined based on multiple single-nucleotide polymorphisms identified in genome-wide association studies of NAFLD. The primary outcome was change in LPR between baseline and follow-up measurement. RESULTS:For each 1 standard deviation increase in MDS, the LPR increased (meaning liver fat decreased) by 0.57 (95% confidence interval [CI] 0.27-0.86; P < .001) and the odds for incident fatty liver decreased by 26% (95% CI 10%-39%; P = .002). For each 1 standard deviation increase in AHEI, LPR increased by 0.56 (95% CI 0.29-0.84; P < .001) and the odds for incident fatty liver decreased by 21% (95% CI 5%-35%; P = .02). Increased diet scores were also associated with reduced odds of developing more-advanced fatty liver. Higher genetic risk scores were associated with increased liver fat accumulation in participants who had decreased MDS (P < .001) or AHEI scores (P = .001), but not in those with stable or improved diet scores (P for gene-diet interaction <.001). CONCLUSIONS:In an analysis of participants in the Framingham Heart Study, increasing diet quality, determined based on MDS and AHEI scores, is associated with less liver fat accumulation and reduced risk for new-onset fatty liver. An improved diet is particularly important for individuals with a high genetic risk for NAFLD.

SUBMITTER: Ma J

PROVIDER: S-EPMC6035111 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease.

Ma Jiantao J Hennein Rachel R Liu Chunyu C Long Michelle T MT Hoffmann Udo U Jacques Paul F PF Lichtenstein Alice H AH Hu Frank B FB Levy Daniel D

Gastroenterology 20180329 1

<h4>Background & aims</h4>Dietary modification has been recommended for treatment of nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent its development. We performed a prospective study to examine the association between diet quality change and change in liver fat. We also examined the association between genetic risk score and liver fat change in individuals with different levels of diet quality change.<h4>Methods</h4>Our study included ...[more]

PMID: 29604292

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Project description:BackgroundAccumulation of saturated fatty acids (SFAs) in the liver is known to induce hepatic steatosis and inflammation causing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although SFAs have been shown to affect the epigenome in whole blood, pancreatic islets, and adipose tissue in humans, and genome-wide DNA methylation studies have linked epigenetic changes to NAFLD and NASH, studies focusing on the association of SFAs and DNA methylation in human liver are missing. We, therefore, investigated whether human liver SFA content associates with DNA methylation and tested if SFA-linked alterations in DNA methylation associate with NAFLD-related clinical phenotypes in obese individuals.ResultsWe identified DNA methylation (Infinium HumanMethylation450 BeadChip) of 3169 CpGs to be associated with liver total SFA content (q-value < 0.05) measured using proton NMR spectroscopy in participants of the Kuopio Obesity Surgery Study (n = 51; mean ± SD:49.3 ± 8.5 years old; BMI:43.7 ± 6.2 kg/m2). Of these 3169 sites, 797 overlapped with previously published NASH-associated CpGs (NASH-SFA), while 2372 CpGs were exclusively associated with SFA (Only-SFA). The corresponding annotated genes of these only-SFA CpGs were found to be enriched in pathways linked to satiety and hunger. Among the 54 genes mapping to these enriched pathways, DNA methylation of CpGs mapping to PRKCA and TSPO correlated with their own mRNA expression (HumanHT-12 Expression BeadChip). In addition, DNA methylation of another ten of these CpGs correlated with the mRNA expression of their neighboring genes (p value < 0.05). The proportion of CpGs demonstrating a correlation of DNA methylation with plasma glucose was higher in NASH-SFA and only-SFA groups, while the proportion of significant correlations with plasma insulin was higher in only-NASH and NASH-SFA groups as compared to all CpGs on the Illumina 450 K array (Illumina, San Diego, CA, USA).ConclusionsOur results suggest that one of the mechanisms how SFA could contribute to metabolic dysregulation in NAFLD is at the level of DNA methylation. We further propose that liver SFA-related DNA methylation profile may contribute more to hyperglycemia, while insulin-related methylation profile is more linked to NAFLD or NASH. Further research is needed to elucidate the molecular mechanisms behind these observations.

Project description:The pathological progression of nonalcoholic fatty liver disease (NAFLD) is driven by multiple factors, and nonalcoholic steatohepatitis (NASH) represents its progressive form. In our previous studies, we found that bicyclol had beneficial effects on NAFLD/NASH. Here we aim to investigate the underlying molecular mechanisms of the bicyclol effect on NAFLD/NASH induced by high-fat diet (HFD) feeding. A mice model of NAFLD/NASH induced by HFD-feeding for 8 weeks was used. As a pretreatment, bicyclol (200 mg/kg) was given to mice by oral gavage twice daily. Hematoxylin and eosin (H&E) stains were processed to evaluate hepatic steatosis, and hepatic fibrous hyperplasia was assessed by Masson staining. Biochemistry analyses were used to measure serum aminotransferase, serum lipids, and lipids in liver tissues. Proteomics and bioinformatics analyses were performed to identify the signaling pathways and target proteins. The real-time RT-PCR and Western blot analyses were performed to verify the proteomics data. As a result, bicyclol had a markedly protective effect against NAFLD/NASH by suppressing the increase of serum aminotransferase, hepatic lipid accumulation and alleviating histopathological changes in liver tissues. Proteomics analyses showed that bicyclol remarkably restored major pathways related to immunological responses and metabolic processes altered by HFD feeding. Consistent with our previous results, bicyclol significantly inhibited inflammation and oxidative stress pathway related indexes (SAA1, GSTM1 and RDH11). Furthermore, the beneficial effects of bicyclol were closely associated with the signaling pathways of bile acid metabolism (NPC1, SLCOLA4 and UGT1A1), cytochrome P450-mediated metabolism (CYP2C54, CYP2C70 and CYP3A25), biological processes such as metal ion metabolism (Ceruloplasmin and Metallothionein-1), angiogenesis (ALDH1A1) and immunological responses (IFI204 and IFIT3). These findings suggested that bicyclol is a potential preventive agent for NAFLD/NASH by targeting multiple mechanisms in future clinical investigations.

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Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease.

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Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease.

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