Genetic Factors Associated with Response to Vitamin E Treatment in NAFLD

Civelek, Mehtap; Podszun, Maren C.

doi:10.3390/antiox11071284

Cited by 9 publications

(5 citation statements)

References 88 publications

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“…Consequently, this may be one of the contributing factors to the distinctive lipid metabolism characteristics observed in goose liver tissue. Moreover, FADS1 and FADS2 are two rate-controlling enzymes in de novo fatty acid synthesis and TG metabolism, and the two genes are potential targets therapeutic targets for NAFLD disease [ 62 , 63 ], serving as pivotal fatty acid desaturases in the process of de novo lipogenesis and ensuing steatosis within goose liver [ 64 ]. The knockdown of FADS1 in the HepG2 cell line resulted in a notable reduction in cellular levels of LC-PUFAs.…”

Section: Discussionmentioning

confidence: 99%

Exploring the dynamic three-dimensional chromatin architecture and transcriptional landscape in goose liver tissues underlying metabolic adaptations induced by a high-fat diet

Gao,

Liu,

et al. 2024

J Animal Sci Biotechnol

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Background Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant energy intake. As a result, goose offers an excellent model for studying obesity, metabolic disorders, and liver diseases in mammals. Although the impact of the three-dimensional arrangement of chromatin within the cell nucleus on gene expression and transcriptional regulation is widely acknowledged, the precise functions of chromatin architecture reorganization during fat deposition in goose liver tissues still need to be fully comprehended. Results In this study, geese exhibited more pronounced changes in the liver index and triglyceride (TG) content following the consumption of the high-fat diet (HFD) than mice without significant signs of inflammation. Additionally, we performed comprehensive analyses on 10 goose liver tissues (5 HFD, 5 normal), including generating high-resolution maps of chromatin architecture, conducting whole-genome gene expression profiling, and identifying H3K27ac peaks in the livers of geese and mice subjected to the HFD. Our results unveiled a multiscale restructuring of chromatin architecture, encompassing Compartment A/B, topologically associated domains, and interactions between promoters and enhancers. The dynamism of the three-dimensional genome architecture, prompted by the HFD, assumed a pivotal role in the transcriptional regulation of crucial genes. Furthermore, we identified genes that regulate chromatin conformation changes, contributing to the metabolic adaptation process of lipid deposition and hepatic fat changes in geese in response to excessive energy intake. Moreover, we conducted a cross-species analysis comparing geese and mice exposed to the HFD, revealing unique characteristics specific to the goose liver compared to a mouse. These chromatin conformation changes help elucidate the observed characteristics of fat deposition and hepatic fat regulation in geese under conditions of excessive energy intake. Conclusions We examined the dynamic modifications in three-dimensional chromatin architecture and gene expression induced by an HFD in goose liver tissues. We conducted a cross-species analysis comparing that of mice. Our results contribute significant insights into the chromatin architecture of goose liver tissues, offering a novel perspective for investigating mammal liver diseases.

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Section: Discussionmentioning

confidence: 99%

Exploring the dynamic three-dimensional chromatin architecture and transcriptional landscape in goose liver tissues underlying metabolic adaptations induced by a high-fat diet

Gao,

Liu,

et al. 2024

J Animal Sci Biotechnol

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“…It can also enhance the liver decompensation period and improve liver transplant-free survival in patients with advanced fibrosis due to NAFLD [56][57][58] . Currently, it is assumed that genetic variants in haptoglobin and fatty acid desaturase 1/2 (FADS1/FADS2) may contribute to the different treatment responses of vitamin E in patients with NAFLD 59 . Considering that vitamin E may improve non-alcoholic steatohepatitis (NASH) symptoms in some nondiabetic patients, the American Association for the Study of Liver Diseases (AASLD) recommends that vitamin E be used in this specific group of individuals 60 .…”

Section: Discussionmentioning

confidence: 99%

Association between the composite dietary antioxidant index and metabolic dysfunction-associated steatotic liver disease in adults: a cross-sectional study from NHANES 2017–2020

Yang,

Song,

et al. 2024

Sci Rep

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Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a predominant liver disease worldwide, lacking approved drugs for clinical intervention at present. The composite dietary antioxidant index (CDAI) is used to assess the anti-inflammatory properties of diets, with higher CDAI indicating greater exposure to antioxidants. Therefore, our study aimed to explore the relationship between CDAI and MASLD in order to identify potential therapeutic approaches. We collected data from 12,286 participants in the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020 for analysis. The correlation between CDAI and MASLD status, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) was evaluated by adjusting for confounding variables using weighted binary logistic regression model, linear regression model, and restricted cubic spline (RCS) regression. The median CDAI in this study was − 0.3055 (interquartile range [IQR], − 2.299 to 2.290). The CDAI was higher in the population characterized by being young, female, higher income, absence of diabetes, and non-MASLD. After multivariable adjustment, the results of the weighted linear regression model suggested that higher CDAI may be associated with a decrease in CAP values; the results of the RCS regression model indicated significant non-linear relationships between MASLD status, CAP, LSM, and CDAI. The CDAI corresponding to the inflection points of the relationship curves between MASLD status, CAP, LSM, and CDAI were 0.349, 0.699, and 0.174, respectively. After further stratification by gender, we found that the relationship between MASLD status, CAP, and CDAI was significantly linear for females, whereas for males, it was non-linear, and the CDAI values corresponding to the inflection points in the curves for males were 1.325 and 0.985, respectively. We found that higher CDAI may be associated with decreased CAP values, particularly significant in females, suggesting that the intake of complex dietary antioxidants may ameliorate hepatic steatosis and reduce the occurrence of MASLD. Therefore, promoting dietary patterns rich in antioxidants may be an appropriate strategy to reduce the incidence of MASLD.

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“…Vitamin E enhances the activity of the antioxidant enzymes catalase and glutathione peroxidase [ 113 ]. Furthermore, genetic factors, including variations in haptoglobin and fatty acid desaturase 1/2 (FADS1/FADS2), may influence the therapeutic efficacy of Vitamin E in NAFLD [ 114 ]. Clinical studies have demonstrated Vitamin E ameliorates liver fibrosis in patients with NASH [ 115 ].…”

Section: Pharmacological Treatment Of Nafld In Western Medicinementioning

confidence: 99%

Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies

Ding,

He,

Tang

et al. 2024

Chin Med

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Traditional Chinese medicine (TCM) has been widely used for several centuries for metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). At present, NAFLD has become the most prevalent form of chronic liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. However, there is still a lack of effective treatment strategies in Western medicine. The development of NAFLD is driven by multiple mechanisms, including genetic factors, insulin resistance, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, gut microbiota dysbiosis, and adipose tissue dysfunction. Currently, certain drugs, including insulin sensitizers, statins, vitamin E, ursodeoxycholic acid and betaine, are proven to be beneficial for the clinical treatment of NAFLD. Due to its complex pathogenesis, personalized medicine that integrates various mechanisms may provide better benefits to patients with NAFLD. The holistic view and syndrome differentiation of TCM have advantages in treating NAFLD, which are similar to the principles of personalized medicine. In TCM, NAFLD is primarily classified into five types based on clinical experience. It is located in the liver and is closely related to spleen and kidney functions. However, due to the multi-component characteristics of traditional Chinese medicine, its application in the treatment of NAFLD has been considerably limited. In this review, we summarize the advances in the pathogenesis and treatment of NAFLD, drawn from both the Western medicine and TCM perspectives. We highlight that Chinese and Western medicine have complementary advantages and should receive increased attention in the prevention and treatment of NAFLD.

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Genetic Factors Associated with Response to Vitamin E Treatment in NAFLD

Cited by 9 publications

References 88 publications

Exploring the dynamic three-dimensional chromatin architecture and transcriptional landscape in goose liver tissues underlying metabolic adaptations induced by a high-fat diet

Exploring the dynamic three-dimensional chromatin architecture and transcriptional landscape in goose liver tissues underlying metabolic adaptations induced by a high-fat diet

Association between the composite dietary antioxidant index and metabolic dysfunction-associated steatotic liver disease in adults: a cross-sectional study from NHANES 2017–2020

Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies

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