Apart from the known associations between arachidonic acid (AA), weight gain, and neurological and immune function, AA exposure leads to alterations in global and gene-specific DNA methylation (DNAm) and fatty acid (FA) content in human cultured cells. However, it is unknown as to whether the latter effects occur in vivo and are maintained over extended periods of time and across generations. To address this issue, we asked whether AA supplementation for three consecutive generations (prior to coitus in sires or in utero in dams) affected offspring growth phenotypes, in addition to liver DNAm and FA profiles in mice. Twelve-week-old BALB/c mice were exposed daily to AA dissolved in soybean oil (vehicle, VH), or VH only, for 10 days prior to mating or during the entire pregnancy (20 days). On average, 15 mice were supplemented per generation, followed by analysis of offspring body weight and liver traits (x average = 36 and 10 per generation, respectively). Body weight cumulatively increased in F2 and F3 offspring generations and positively correlated with milligrams of paternal or maternal offspring AA exposure. A concomitant increase in liver weight was observed. Notably, akin to AA-challenged cultured cells, global DNAm and cis-7-hexadecenoic acid (16:1n-9), an anti-inflammatory FA that is dependent on stearoyl-CoA desaturase 1 (SCD1) activity, increased with milligrams of AA exposure. In accordance, liver Scd1 promoter methylation decreased with milligrams of germline AA exposure and was negatively correlated with liver weight. Our results show that mice retain cellular memories of AA exposure across generations that could potentially be beneficial to the innate immune system.

Increasing evidence hints that DNA hypermethylation may mediate the pathogenic response to cardiovascular risk factors. Here, we tested a corollary of that hypothesis, that is, that the DNA methyltransferase inhibitor decitabine (Dec) ameliorates the metabolic profile of mice fed a moderately high-animal fat and protein diet (HAFPD), a proxy of cardiovascular risk-associated Western-type diet. HAFPD-fed mice were exposed to Dec or vehicle for eight weeks (8W set, 4-32/group). To assess any memory of past exposure to Dec, we surveyed a second mice set treated as 8W but HAFPD-fed for further eight weeks without any Dec (16W set, 4-20/group). In 8W, Dec markedly reduced HAFPD-induced body weight gain in females, but marginally in males. Characterization of females revealed that Dec augmented skeletal muscle lipid content, while decreasing liver fat content and increasing plasma nonesterified fatty acids, adipose insulin resistance, and-although marginally-whole blood acylcarnitines, compared to HAFPD alone. Skeletal muscle mitochondrial DNA copy number was higher in 8W mice exposed to HAFPD and Dec, or in 16W mice fed HAFPD only, relative to 8W mice fed HAFPD only, but Dec induced a transcriptional profile indicative of ameliorated mitochondrial function. Memory of past Dec exposure was tissue-specific and sensitive to both duration of exposure to HAFPD and age. In conclusion, Dec redirected HAFPD-induced lipid accumulation toward the skeletal muscle, likely due to augmented mitochondrial functionality and increased lipid demand. As caveat, Dec induced adipose insulin resistance. Our findings may help identifying strategies for prevention and treatment of lipid dysmetabolism.

Background/Objectives: The inflammatory response has evolved as a protective mechanism against pathogens and tissue damage. However, chronic inflammation can occur, potentially leading to severe disease. Low-grade chronic inflammation is associated with obesity, and the Th1 cytokine profile plays an important role in this proinflammatory environment. Diet-induced obesity (DIO) can lead to persistent dysbiosis and maintain high concentrations of circulating lipopolysaccharides (LPSs) over prolonged periods of time, resulting in metabolic endotoxemia. In this context, the study of natural immunomodulators has recently increased. Objective: The aim of this study is improve scientific evidence for the immunomodulatory role of L-Alliin in obesity and inflammation. Methods: In the present work, we describe the effect of L-Alliin on serum levels of cytokines in DIO mice after an acute inflammatory challenge. L-Alliin is the main organosulfurized molecule of garlic that has been studied for its numerous beneficial physiological effects in health and disease and is beginning to be considered a nutraceutical. Two situations are simulated in this experimental model, health and chronic, low-grade inflammation that occurs in obesity, both of which are confronted with an acute, inflammation-inducing challenge. Results: Based on our findings, L-Alliin seems to somehow stimulate the cellular chemotaxis by eliciting the release of key molecules, including IL-2, IFN-γ, TNF-α, MCP-1, IL-6, IL-9, and G-CSF. However, the molecular mechanism involved remains unknown. This, in turn, mitigates the risk of severe inflammatory symptoms by preventing the release of IL-1β and its downstream molecules such as IL-1α, GM-CSF, and RANTES. Conclusions: Taken together, these results indicate that L-Alliin can boost immunity in healthy organisms and act as an immunomodulator in low-grade inflammation.

One of the main pathological features of Alzheimer’s disease (AD) is the accumulation of amyloid β (Aβ) peptides, which is encoded by the amyloid precursor protein (APP) gene. The etiology of sporadic AD (non-familial) remains largely unknown, and genetic mutations explain only about 5–10% of cases. Epigenetic alterations, such as DNA methylation, have been proposed as mechanisms contributing to the overproduction of Aβ, which is associated with aggregation. Differences in methylation in the APP gene has been reported in certain brain regions and blood samples from individuals with AD. Dietary components and natural compounds such as fatty acids, methionine, and folate have been associated with differential methylation and may represent potential therapeutic or preventive strategies for AD. This mini-review discusses available evidence on how specific dietary factors and natural compounds may influence DNA methylation of the APP gene revealing promising directions for nutrition-oriented prevention strategies.

Background: Periodontitis continues to be a global public health burden that is associated with an increased risk of metabolic diseases such as type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases. Several studies, unsystematized, have evaluated the relationship between consumption of specific foods, nutrients, or eating patterns and the disease, aiming to support personalized and holistic periodontal therapy. Objective: This scoping review aimed to evaluate which dietary intakes are linked to the pathology. Methods: The scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search was conducted in PubMed. The inclusion criteria were original studies with adult populations that evaluated diet and nutrient intake in populations with periodontitis. Results: Thirty-six articles were included (26 cross-sectional, 6 cohort studies, 3 randomized clinical trials, and 1 case–control). Specifically, adequate protein intake significantly reduced bleeding on probing, while high fiber intake was inversely associated with alveolar bone loss and tooth loss. Furthermore, higher consumption of vitamins C and D correlated with a reduced periodontitis risk. Negative associations were observed between nutrient groups (vitamin A, C, E, K, flavonoid, fiber) and plant-based food groups (green–yellow vegetables, general vegetables, fruit) and community periodontal index, tooth loss, probing depth, and clinical attachment loss. Broader diet quality also mattered: adherence to healthy anti-inflammatory dietary patterns were consistently associated with lower periodontitis risk, whereas pro-inflammatory patterns were in the opposite direction. Conclusions: This review strengthens the importance of the links between single nutrients, food groups, and eating patterns in periodontitis. Integrating personalized nutritional advice into dental settings represents a valuable host-modulating strategy to optimize periodontal therapy outcomes.