Among cardiovascular disease (CVD) biomarkers, the mitochondrial DNA copy number (mtDNAcn) is a promising candidate. A growing attention has been also dedicated to trimethylamine‐N‐oxide (TMAO), an oxidative derivative of the gut metabolite trimethylamine (TMA). With the aim to identify biomarkers predictive of CVD, we investigated TMA, TMAO, and mtDNAcn in a population of 389 coronary artery disease (CAD) patients and 151 healthy controls, in association with established risk factors for CVD (sex, age, hypertension, smoking, diabetes, glomerular filtration rate [GFR]) and troponin, an established marker of CAD. MtDNAcn was significantly lower in CAD patients; it correlates with GFR and TMA, but not with TMAO. A biomarker including mtDNAcn, sex, and hypertension (but neither TMA nor TMAO) emerged as a good predictor of CAD. Our findings support the mtDNAcn as a promising plastic biomarker, useful to monitor the exposure to risk factors and the efficacy of preventive interventions for a personalized CAD risk reduction.

Mitochondrial DNA copy number (mtDNAcn) has been proposed for use as a surrogate biomarker of mitochondrial health, and evidence suggests that mtDNA might be methylated. Intermediates of the one-carbon cycle (1CC), which is duplicated in the cytoplasm and mitochondria, have a major role in modulating the impact of diet on the epigenome. Moreover, epigenetic pathways and the redox system are linked by the metabolism of glutathione (GSH). In a cohort of 101 normal-weight and 97 overweight/obese subjects, we evaluated mtDNAcn and methylation levels in both mitochondrial and nuclear areas to test the association of these marks with body weight, metabolic profile, and availability of 1CC intermediates associated with diet. Body composition was associated with 1CC intermediate availability. Reduced levels of GSH were measured in the overweight/obese group ( p = 1.3 ∗ 10 − 5 ). A high BMI was associated with lower LINE-1 ( p = 0.004 ) and nominally lower methylenetetrahydrofolate reductase (MTHFR) gene methylation ( p = 0.047 ). mtDNAcn was lower in overweight/obese subjects ( p = 0.004 ) and independently correlated with MTHFR methylation levels ( p = 0.005 ) but not to LINE-1 methylation levels ( p = 0.086 ). DNA methylation has been detected in the light strand but not in the heavy strand of the mtDNA. Although mtDNA methylation in the light strand did not differ between overweight/obese and normal-weight subjects, it was nominally correlated with homocysteine levels ( p = 0.035 ) and MTHFR methylation ( p = 0.033 ). This evidence suggests that increased body weight might perturb mitochondrial-nuclear homeostasis affecting the availability of nutrients acting as intermediates of the one-carbon cycle.

Dietary lipids have a major role in nutrition, not only for their fuel value, but also as essential and bioactive nutrients. This narrative review aims to describe the current evidence on nutrigenomic effects of dietary lipids. Firstly, the different chemical and biological properties of fatty acids contained both in plant- and animal-based food are illustrated. A description of lipid bioavailability, bioaccessibility, and lipotoxicity is provided, together with an overview of the modulatory role of lipids as pro- or anti-inflammatory agents. Current findings concerning the metabolic impact of lipids on gene expression, epigenome, and gut microbiome in animal and human studies are summarized. Finally, the effect of the individual’s genetic make-up on lipid metabolism is described. The main goal is to provide an overview about the interaction between dietary lipids and the genome, by identifying and discussing recent scientific evidence, recognizing strengths and weaknesses, to address future investigations and fill the gaps in the current knowledge on metabolic impact of dietary fats on health.

Antioxidant peptides extracted from natural foods have been studied for their potential use in the development of additives, nutraceuticals, and therapeutic agents. Nut proteins are considered an excellent source of plant-derived proteins for the human diet, due to their high protein content and digestibility of up to 86.22%. Furthermore, compared with grain and soybean proteins, nut proteins have a special amino acid composition, which makes their protein structure different, and promotes their disparate functional characteristics and great bioactivity potential. This review presents the most remarkable studies on antioxidant peptides from nuts, to gain insights into feasible production methods, different evaluation indexes within in vivo or in vitro systems, high bioavailability, and the complex structure-activity relationship resulting from the particularity of their protein structure and amino acid composition. Previously published studies mainly focused on the effects of the production methods/processes of nut-derived peptides on antioxidant activity, and proved that nut-extracted antioxidant peptides can resist the degradation of acid, alkali, and gastrointestinal enzymes, have high antioxidant activity in vitro and in vivo, and also have the potential to cross small intestinal epithelial cells in a stable and integral manner. However, the structure-activity relationship of antioxidant peptides from nuts has not been fully established, and the structure information of antioxidant peptides obtained from various nut protein sources is still unclear. The findings presented in this review can be used to provide the theoretical basis for the design and production of nut-derived antioxidant peptides.

Physical activity represents a powerful tool to achieve optimal health. The overall activation of several molecular pathways is associated with many beneficial effects, mainly converging towards a reduced systemic inflammation. Not surprisingly, regular activity can contribute to lowering the “epigenetic age”, acting as a modulator of risk toward several diseases and enhancing longevity. Behind this, there are complex molecular mechanisms induced by exercise, which modulate gene expression, also through epigenetic modifications. The exercise-induced epigenetic imprint can be transient or permanent and contributes to the muscle memory, which allows the skeletal muscle adaptation to environmental stimuli previously encountered. Nutrition, through key macro- and micronutrients with antioxidant properties, can play an important role in supporting skeletal muscle trophism and those molecular pathways triggering the beneficial effects of physical activity. Nutrients and antioxidant food components, reversibly altering the epigenetic imprint, have a big impact on the phenotype. This assigns a role of primary importance to nutri(epi)genomics, not only in optimizing physical performance, but also in promoting long term health. The crosstalk between physical activity and nutrition represents a major environmental pressure able to shape human genotypes and phenotypes, thus, choosing the right combination of lifestyle factors ensures health and longevity.