Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) refers to the pathologic buildup of extra fat in the form of triglycerides in liver cells without excessive alcohol intake. NAFLD became the most common cause of chronic liver disease that is tightly associated with key aspects of metabolic disorders, including insulin resistance, obesity, diabetes, and metabolic syndrome. It is generally accepted that multiple mechanisms and pathways are involved in the pathogenesis of NAFLD. Heredity, sedentary lifestyle, westernized high sugar saturated fat diet, metabolic derangements, and gut microbiota, all may interact on a on genetically susceptible individual to cause the disease initiation and progression. While there is an unquestionable role for gene-diet interaction in the etiopathogenesis of NAFLD, it is increasingly apparent that epigenetic processes can orchestrate many aspects of this interaction and provide additional mechanistic insight. Exciting research demonstrated that epigenetic alterations in chromatin can influence gene expression chiefly at the transcriptional level in response to unbalanced diet, and therefore predispose an individual to NAFLD. Thus, further discoveries into molecular epigenetic mechanisms underlying the link between nutrition and aberrant hepatic gene expression can yield new insights into the pathogenesis of NAFLD, and allow innovative epigenetic-based strategies for its early prevention and targeted therapies. Herein, we outline the current knowledge of the interactive role of a high-fat high-calories diet and gene expression through DNA methylation and histone modifications on the pathogenesis of NAFLD. We also provide perspectives on the advancement of the epigenomics in the field and possible shortcomings and limitations ahead.

AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD

“…DNA methylation is highly dynamic and changes in response to environmental conditions, personal cellular, and tissue microenvironments ( Hyun and Jung, 2020 ; Pogribna and Hammons, 2021 ). DNA methylation profiles of liver biopsies obtained from patients with NAFLD revealed that hepatic DNA methylation altered in NAFLD patients is an important factor for the pathogenesis of NAFLD and the progression of this disease from simple steatosis to NAFLD ( Zaiou et al, 2021 ). Betaine attenuated HFD-induced hepatic steatosis and triglyceride accumulation in mice by alleviating the methylation of microsomal triglyceride transfer protein (MTTP) and peroxisomal proliferator-activated receptor alpha (PPARα) promoter in the liver ( Wang et al, 2013 ; Wang et al, 2014 ), indicating the crucial relationship between DNA methylation and NAFLD development.…”

Deciphering the role of aberrant DNA methylation in NAFLD and NASH

“…“ Nutriepigenomics” a fast-evolving field that involves the study of nutrient-genome interactions via epigenetic alterations is rapidly gaining prominence in various complex human disorders [ 153 , 154 ]. Food intake influences epigenome remodeling considerably all throughout life.…”

Histone Demethylation Profiles in Nonalcoholic Fatty Liver Disease and Prognostic Values in Hepatocellular Carcinoma: A Bioinformatic Analysis

“…Epigenetic regulation in NAFLD mainly comprises DNA methylation, histone modifications, and noncoding RNAs [ 9 , 10 , 11 ]. Histone modifications are mediated via the transfer or removal of amino acid residues from the histone tails by some enzymes [ 12 ]. As a form of histone modification, histone demethylation activates or represses gene expression by removing methyl groups from modified histones through histone demethylases (HDMs).…”