Metabolo-epigenetic interplay provides targeted nutritional interventions in chronic diseases and ageing

Abstract

Epigenetic modifications are chemical modifications that affect gene expression without altering DNA sequences. In particular, epigenetic chemical modifications can occur on histone proteins -mainly acetylation, methylation-, and on DNA and RNA molecules -mainly methylation-. Additional mechanisms, such as RNA-mediated regulation of gene expression and determinants of the genomic architecture can also affect gene expression. Importantly, depending on the cellular context and environment, epigenetic processes can drive developmental programs as well as functional plasticity. However, misbalanced epigenetic regulation can result in disease, particularly in the context of metabolic diseases, cancer, and ageing. Non-communicable chronic diseases (NCCD) and ageing share common features including altered metabolism, systemic meta-inflammation, dysfunctional immune system responses, and oxidative stress, among others. In this scenario, unbalanced diets, such as high sugar and high saturated fatty acids consumption, together with sedentary habits, are risk factors implicated in the development of NCCD and premature ageing. The nutritional and metabolic status of individuals interact with epigenetics at different levels. Thus, it is crucial to understand how we can modulate epigenetic marks through both lifestyle habits and targeted clinical interventions -including fasting mimicking diets, nutraceuticals, and bioactive compounds- which will contribute to restore the metabolic homeostasis in NCCD. Here, we first describe key metabolites from cellular metabolic pathways used as substrates to “write” the epigenetic marks; and cofactors that modulate the activity of the epigenetic enzymes; then, we briefly show how metabolic and epigenetic imbalances may result in disease; and, finally, we show several examples of nutritional interventions - diet based interventions, bioactive compounds, and nutraceuticals- and exercise to counteract epigenetic alterations.

Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD

“…For example, several interventions may include diets low in carbohydrates, free sugars, fructose, and lipids, in addition to healthy eating patterns and probiotics [32]. At diverse levels, the nutritional and metabolic status of individuals may interact with epigenetics, which are chemical modifications that affect gene expression without altering DNA sequences [33]. Therefore, it is important to understand how we can control epigenetic characteristics through both lifestyle habits and some clinical interventions.…”

“…Therefore, it is important to understand how we can control epigenetic characteristics through both lifestyle habits and some clinical interventions. Misbalanced epigenetic regulation can result in various metabolic diseases and/or aging [33]. Epigenetic modifications are potentially reversible and can provide new therapeutic avenues for treating these diseases using epigenetic modulators [34].…”

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies

“…In PE, reduced placental blood flow causes hypoxia and results in epigenetic changes that activate adaptive responses in the placenta and maternal circulation [ 89 , 90 ]. Nutrition, diet, and metabolism regulate epigenetic mechanisms and integrate environmental cues and exposures with cellular responses [ 91 ]. Cellular metabolites (acetyl coenzyme A, adenosine triphosphate, nicotinamide adenine dinucleotide) act as nutrient sensors and contribute to the regulation of gene expression via epigenetic mechanisms [ 92 ].…”

“…Cellular metabolites (acetyl coenzyme A, adenosine triphosphate, nicotinamide adenine dinucleotide) act as nutrient sensors and contribute to the regulation of gene expression via epigenetic mechanisms [ 92 ]. Reciprocal crosstalk between epigenetics and metabolism determines molecular programming and cellular function [ 91 ]. Maternal obesity can lead to placental dysfunction via chronic inflammation, the dysregulation of metabolic pathways, and epigenetic changes in gene expression [ 93 , 94 ].…”

Nutrigenomics and redox regulation: Concepts relating to the Special Issue on nutrigenomics

“…Moreover, the epigenome of metabolic organs, such as skeletal muscle and adipose tissue, is able to memorize nutrient availability and energy status of the body and adapt accordingly, i.e. , these tissues “memorize” and integrate via changes of epigenetic patterns in the level of DNA methylation, histone modifications and 3D chromatin structure how much we have eaten and how much physical activity we have had [ 50 ]. For example, in caloric restriction, i.e.…”