DNA methylation is an epigenetic mechanism that is essential for regulating gene transcription. However, aberrant DNA methylation, which is a nearly universal finding in cancer, can result in disturbed gene expression. DNA methylation is modified by environmental factors such as diet that may modify cancer risk and tumor behavior. Abnormal DNA methylation has been observed in several cancers such as colon, stomach, cervical, prostate, and breast cancers. These alterations in DNA methylation may play a critical role in cancer development and progression. Dietary nutrient intake and bioactive food components are essential environmental factors that may influence DNA methylation either by directly inhibiting enzymes that catalyze DNA methylation or by changing the availability of substrates required for those enzymatic reactions such as the availability and utilization of methyl groups. In this review, we focused on nutrients that act as methyl donors or methylation co-factors and presented intriguing evidence for the role of these bioactive food components in altering DNA methylation patterns in cancer. Such a role is likely to have a mechanistic impact on the process of carcinogenesis and offer possible therapeutic potentials.

Obesity has become a global epidemic that has a negative impact on population health and the economy of nations. Genetic predispositions have been demonstrated to have a substantial role in the unbalanced energy metabolism seen in obesity. However, these genetic variations cannot entirely explain the massive growth in obesity over the last few decades. Accumulating evidence suggests that modern lifestyle characteristics such as the intake of energy-dense foods, adopting sedentary behavior, or exposure to environmental factors such as industrial endocrine disruptors all contribute to the rising obesity epidemic. Recent advances in the study of DNA and its alterations have considerably increased our understanding of the function of epigenetics in regulating energy metabolism and expenditure in obesity and metabolic diseases. These epigenetic modifications influence how DNA is transcribed without altering its sequence. They are dynamic, reflecting the interplay between the body and its surroundings. Notably, these epigenetic changes are reversible, making them appealing targets for therapeutic and corrective interventions. In this review, I discuss how these epigenetic modifications contribute to the disordered energy metabolism in obesity and to what degree lifestyle and weight reduction strategies and pharmacological drugs can restore energy balance by restoring normal epigenetic profiles.

Adipose tissue was previously regarded as a dormant organ for lipid storage until the identification of adiponectin and leptin in the early 1990s. This revelation unveiled the dynamic endocrine function of adipose tissue, which has expanded further. Adipose tissue has emerged in recent decades as a multifunctional organ that plays a significant role in energy metabolism and homeostasis. Currently, it is evident that adipose tissue primarily performs its function by secreting a diverse array of signaling molecules known as adipokines. Apart from their pivotal function in energy expenditure and metabolism regulation, these adipokines exert significant influence over a multitude of biological processes, including but not limited to inflammation, thermoregulation, immune response, vascular function, and insulin sensitivity. Adipokines are pivotal in regulating numerous biological processes within adipose tissue and facilitating communication between adipose tissue and various organs, including the brain, gut, pancreas, endothelial cells, liver, muscle, and more. Dysregulated adipokines have been implicated in several metabolic diseases, like obesity and diabetes, as well as cardiovascular diseases. In this article, we attempted to describe the significance of adipokines in developing metabolic and cardiovascular diseases and highlight their role in the crosstalk between adipose tissues and other tissues and organs.

Breast cancer formation is associated with frequent changes in DNA methylation but the extent of very early alterations in DNA methylation and the biological significance of cancer-associated epigenetic changes need further elucidation. Pyrosequencing was done on bisulfite-treated DNA from formalin-fixed, paraffin-embedded sections containing invasive tumor and paired samples of histologically normal tissue adjacent to the cancers as well as control reduction mammoplasty samples from unaffected women. The DNA regions studied were promoters (BRCA1, CD44, ESR1, GSTM2, GSTP1, MAGEA1, MSI1, NFE2L3, RASSF1A, RUNX3, SIX3 and TFF1), far-upstream regions (EN1, PAX3, PITX2, and SGK1), introns (APC, EGFR, LHX2, RFX1 and SOX9) and the LINE-1 and satellite 2 DNA repeats. These choices were based upon previous literature or publicly available DNA methylome profiles. The percent methylation was averaged across neighboring CpG sites. Most of the assayed gene regions displayed hypermethylation in cancer vs. adjacent tissue but the TFF1 and MAGEA1 regions were significantly hypomethylated (p ≤0.001). Importantly, six of the 16 regions examined in a large collection of patients (105 – 129) and in 15-18 reduction mammoplasty samples were already aberrantly methylated in adjacent, histologically normal tissue vs. non-cancerous mammoplasty samples (p ≤0.01). In addition, examination of transcriptome and DNA methylation databases indicated that methylation at three non-promoter regions (far-upstream EN1 and PITX2 and intronic LHX2) was associated with higher gene expression, unlike the inverse associations between cancer DNA hypermethylation and cancer-altered gene expression usually reported. These three non-promoter regions also exhibited normal tissue-specific hypermethylation positively associated with differentiation-related gene expression (in muscle progenitor cells vs. many other types of normal cells). The importance of considering the exact DNA region analyzed and the gene structure was further illustrated by bioinformatic analysis of an alternative promoter/intron gene region for APC. We confirmed the frequent DNA methylation changes in invasive breast cancer at a variety of genome locations and found evidence for an extensive field effect in breast cancer. In addition, we illustrate the power of combining publicly available whole-genome databases with a candidate gene approach to study cancer epigenetics.