Genetic Variability Impacts Genotoxic and Transcriptome Responses in the Human Colon after the Consumption of Processed Red Meat Products and Those with Added Phytochemical Extracts.

The PHYTOME study investigated the effect of consuming processed meat products on outcomes related to colorectal cancer risk without testing the impact of genetic variability on these responses. This research aims to elucidate the genetic impact on apparent total N-nitroso compound (ATNC) excretion, colonic DNA adduct formation, ex vivo-induced DNA damage, and gene expression changes in colon biopsies of healthy participants. Through a systematic literature review, candidate polymorphisms were selected and then detected using TaqMan and PCR analysis. The effect of genotype on study outcomes was determined via a linear mixed model and analysis of variance. Machine learning was used to evaluate relative allele importance concerning genotoxic responses, which established a ranking of the most protective alleles and a combination of genotypes (gene scores). Participants were grouped by GSTM1 genotype and differentially expressed genes (DEGs), and overrepresented biological pathways were compared between groups. Stratifying participants by ten relevant genes revealed significant variations in outcome responses. After consumption of processed red meat, variations in NQO1 and COMT impacted responses in ATNC levels (µmol/L) (+9.56 for wildtype vs. heterozygous) and DNA adduct levels (pg/µg DNA) (+1.26 for variant vs. wildtype and +0.43 for variant vs. heterozygous), respectively. After phytochemicals were added to the meat, GSTM1 variation impacted changes in DNA adduct levels (-6.12 for deletion vs. wildtype). The gene scores correlated with these responses and DEGs were identified by GSTM1 genotype. The altered pathways specific to the GSTM1 wildtype group included 'metabolism', 'cell cycle', 'vitamin D receptor', and 'metabolism of water-soluble vitamins and co-factors'. Genotype impacted both the potential genotoxicity of processed red meat and the efficacy of protective phytochemical extracts.

Impact of Processing Method and Storage Time on Phytochemical Concentrations in an Antioxidant-Rich Food Mixture.

Foods high in phytochemicals are known for their role in the prevention of chronic disease development, but after processing and storage, such food products may lose part of their functionality as these compounds are sensitive to the impact of processing temperature and the type of methods applied. Therefore, we measured the levels of vitamin C, anthocyanins, carotenoids, catechins, chlorogenic acid, and sulforaphane in a complex blend of fruits and vegetables, and when applied to a dry food product, after exposure to different processing methods. These levels were compared between pasteurized, pascalized (high-pressure processing), and untreated conditions. Furthermore, we established the effect of freezing and storage time on the stability of these compounds. The results showed that pascalization better preserved vitamin C and sulforaphane, whereas pasteurization resulted in higher concentrations of chlorogenic acid, carotenoids, and catechins. For samples which were frozen and thawed immediately after processing, pascalization was the optimal treatment for higher contents of lutein, cyanidin-3-glucoside, quercetin-3-glucoside, delphinidin-3-glucoside, peonidin-3-glucoside, and epicatechin gallate. Ultimately, the optimal processing method to preserve phytochemicals in fruit and vegetable products is as complex as the blend of compounds, and this decision-making would best be led by the prioritized nutrient aim of an antioxidant food product.

Glutamatergic projections from homeostatic to hedonic brain nuclei regulate intake of highly palatable food.

Food intake is a complex behavior regulated by discrete brain nuclei that integrate homeostatic nutritional requirements with the hedonic properties of food. Homeostatic feeding (i.e. titration of caloric intake), is typically associated with hypothalamic brain nuclei, including the paraventricular nucleus of the hypothalamus (PVN). Hedonic feeding is driven, in part, by the reinforcing properties of highly palatable food (HPF), which is mediated by the nucleus accumbens (NAc). Dysregulation of homeostatic and hedonic brain nuclei can lead to pathological feeding behaviors, namely overconsumption of highly palatable food (HPF), that may drive obesity. Both homeostatic and hedonic mechanisms of food intake have been attributed to several brain regions, but the integration of homeostatic and hedonic signaling to drive food intake is less clear, therefore we aimed to identify the neuroanatomical, functional, and behavioral features of a novel PVN → NAc circuit. Using viral tracing techniques, we determined that PVN → NAc has origins in the parvocellular PVN, and that PVN → NAc neurons express VGLUT1, a marker of glutamatergic signaling. Next, we pharmacogenetically stimulated PVN → NAc neurons and quantified both gamma-aminobutyric acid (GABA) and glutamate release and phospho-cFos expression in the NAc and observed a robust and significant increase in extracellular glutamate and phospho-cFos expression. Finally, we pharmacogenetically stimulated PVN → NAc which decreased intake of highly palatable food, demonstrating that this glutamatergic circuitry regulates aspects of feeding.