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.

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.

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.

Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are the most common forms of dementia globally. AD is characterized by the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau in the brain, leading to progressive memory loss and cognitive decline, significantly impairing daily life. In contrast, FTD is marked by selective degeneration of the frontal and/or temporal lobes, typically resulting in profound changes in personality and social behavior, speech disorders, and psychiatric symptoms. Numerous studies have found microRNAs (miRNAs)—small, non-coding RNA molecules that regulate gene expression post-transcriptionally—to be dysregulated in AD and FTD. As a result, miRNAs have emerged as promising novel biomarkers for these diseases. This review examines the current understanding of miRNAs in AD and FTD, emphasizing their potential as accessible, noninvasive biomarkers for diagnosing these prevalent neurodegenerative disorders.

Trimethylamine (TMA), a byproduct of gut microbiota metabolism from dietary precursors, is not only the precursor of trimethylamine-N-oxide (TMAO) but may also affect gut health. An in vitro model of intestinal epithelium of Caco-2 cells was used to evaluate the impact of TMA on inflammation, paracellular permeability, epigenetics and mitochondrial functions. The expression levels of pro-inflammatory cytokines (IL-6, IL-1β) increased significantly after 24 h exposure to TMA 1 mM. TMA exposure was associated with an upregulation of SIRT1 (TMA 1 mM, 400 μM, 10 μM) and DNMT1 (TMA 1 mM, 400 µM) genes, while DNMT3A expression decreased (TMA 1 mM). In a cell-free model, TMA (from 0.1 µM to 1 mM) induced a dose-dependent reduction in Sirtuin enzyme activity. In Caco-2 cells, TMA reduced total ATP levels and significantly downregulated ND6 expression (TMA 1 mM). TMA excess (1 mM) reduced intracellular mitochondrial DNA copy numbers and increased the methylation of the light-strand promoter in the D-loop area of mtDNA. Also, TMA (1 mM, 400 µM, 10 µM) increased the permeability of Caco-2 epithelium, as evidenced by the reduced transepithelial electrical resistance values. Based on our preliminary results, TMA excess might promote inflammation in intestinal cells and disturb epigenetic and mitochondrial homeostasis.