Epigenetics and mitochondrial dysfunction insights into the impact of the progression of non‐alcoholic fatty liver disease

Abstract

A metabolic problem occurs when regular functions of the body are disrupted due to an undesirable imbalance. Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common in this category. NAFLD is subclassified and progresses from lipid accumulation to cirrhosis before advancing to hepatocellular cancer. In spite of being a critical concern, the standard treatment is inadequate. Metformin, silymarin, and other nonspecific medications are used in the management of NAFLD.Aside from this available medicine, maintaining a healthy lifestyle has been emphasized as a means of combating this. Epigenetics, which has been attributed to NAFLD, is another essential feature of this disease that has emerged as a result of several sorts of research. The mechanisms by which DNA methylation, noncoding RNA, and histone modification promote NAFLD have been extensively researched.Another organelle, mitochondria, which play a pivotal role in biological processes, contributes to the global threat. Individuals with NAFLD have been documented to have a multitude of alterations and malfunctioning. Mitochondria are mainly concerned with the process of energy production and regulation of the signaling pathway on which the fate of a cell relies. Modulation of mitochondria leads to elevated lipid deposition in the liver. Further, changes in oxidation states result in an impaired balance between the antioxidant system and reactive oxygen species directly linked to mitochondria. Hence mitochondria have a definite role in potentiating NAFLD. In this regard, it is essential to consider the role of epigenetics as well as mitochondrial contribution while developing a medication or therapy with the desired accuracy.

Chronic stress alters hepatic metabolism and thermodynamic respiratory efficiency affecting epigenetics in C57BL/6 mice

“… 60 However, there is evidence suggesting that changes in the epigenetic landscape contribute to mitochondrial dysfunction. 71 Altered methylation near the mt-Nd6 gene has previously been observed in diabetes or hepatic steatosis where expression negatively correlated to severity. 67 , 72 , 73 Similar to our findings, this hypermethylation was associated with the altered transcription of the corresponding gene in liver biopsies of patients with NASH, emphasizing the regulatory importance of MT-ND6, a subunit of complex I of the mitochondrial respiratory chain.…”

Pharmacological inhibition of p300 ameliorates steatosis, inflammation, and fibrosis in mice with non-alcoholic steatohepatitis

“…At the genetic level, alterations in gene expression play a pivotal role in initiating and advancing the disease. This modulation is largely driven by epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, which impact the expression of genes without altering the DNA sequence itself [ 4 , 5 ].…”

“…Lifestyle factors such as weight gain and lack of physical activity have been shown to impact the pathogenesis of NAFLD through epigenetic mechanisms [ 4 ]. Epigenetic changes intricately participate in modulating multiple processes such as lipid metabolism, insulin sensitivity, mitochondrial function, and redox balance, all of which are relevant to the pathophysiology of NAFLD [ 4 , 5 ]. Because epigenetic modifications are reversible, they offer a flexible interface between an individual and their environment, making them attractive targets for therapeutic interventions [ 6 ].…”

Radiobioinformatics: A novel bridge between basic research and clinical practice for clinical decision support in diffuse liver diseases

“…Epigenetics is the study of changes in gene expression and phenotypic variations that are not the result of changes in DNA sequences [113]. Methylation of DNA and modification of histones are among the most studied epigenetic modifications [114]. DNA methylation is a significant epigenetic modification of cytosine bases in cytosine‐phospho‐guanine (CpG) dinucleotides, called CpG islands [115].…”

“…There is a link between the methylation status of CpG islands and gene suppression, especially when methylation is in the regulatory and promoter regions of genes [115]. Some genes of patients with NAFLD were found to have different methylation levels than the same genes of healthy individuals [114], and a next‐generation sequencing analysis of liver samples showed that patients with NAFLD had significantly lower levels of global DNA methylation than those with healthy controls [115]. In addition, changes in DNA methylation levels were found to be associated with NAFLD progression from mild to advanced and may be highly predictive of fibrosis [116].…”