Nutrigenomics and Cellular Metabolism

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (1 October 2023) | Viewed by 17390

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Guest Editor
Surgical, Oncological and Stomatological Disciplines Department, Medical School, University of Palermo, Palermo, Italy
Interests: nutrient sensing pathways; nutrition and oncology; metabolic treatment in degenerative diseases; lifestyle and longevity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is estimated that 20% of all deaths worldwide are due to suboptimal nutrition (Lancet 2019; 393: 1958-72). It is therefore mandatory to gain a better understanding of the molecular processes involving nutrient pathways and how single substances and mixtures, especially of natural origins, can modulate them, representing promising tools in preventive medicine. The efficacy of nutrient pathway modulation is confirmed by dietary approaches capable of preventing specific diseases (e.g., DASH diet for cardiovascular disease) or increasing overall longevity, such as by restricting calories without malnutrition, fasting mimicking diet and alternate day fasting. In fact, these treatments positively affect disease incidence, progression and overall longevity in animal and cellular models. In addition to these dietary approaches, many natural substances have been demonstrated to affect cellular metabolism, both directly and by means of epigenome modifications. The search for new substances, the molecular characterization of known substances and knowledge on their ability to modify gene expression of single and groups of genes, as well as the safety and efficacy of these molecules when used to prevent single diseases and to affect overall longevity, is thus of critical importance in preventive medicine.

Prof. Dr. Mario G. Mirisola
Guest Editor

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Keywords

  • nutrients
  • epigenome
  • food
  • gene expression
  • nutrient and transcriptome

Published Papers (9 papers)

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Research

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11 pages, 570 KiB  
Article
Predisposition of the Common MC4R rs17782313 Female Carriers to Elevated Obesity and Interaction with Eating Habits
by Danyel Chermon and Ruth Birk
Genes 2023, 14(11), 1996; https://doi.org/10.3390/genes14111996 - 25 Oct 2023
Viewed by 948
Abstract
The global rise in obesity is attributed to genetic predisposition interaction with an obesogenic environment. Melanocortin 4 receptor (MC4R) rs17782313 polymorphism has been linked to common obesity with varying influence across different populations. MC4R is a crucial player in the leptin [...] Read more.
The global rise in obesity is attributed to genetic predisposition interaction with an obesogenic environment. Melanocortin 4 receptor (MC4R) rs17782313 polymorphism has been linked to common obesity with varying influence across different populations. MC4R is a crucial player in the leptin proopiomelanocortin pathway that regulates weight hemostasis. We aimed to study MC4R rs17782313 and its interaction with eating behaviors on obesity predisposition in the Israeli population. Adults’ (n = 5785, >18 y) genotype and anthropometric and demographic data were analyzed using logistic regression models adjusting for age, sex, T1DM, and T2DM. MC4R rs17782313 significantly predisposes to elevated obesity risk under the recessive and additive models (OR = 1.38, 95% CI: 1.1–1.72, p = 0.005 and OR = 1.1, 95% CI: 1.01–1.2, p = 0.03, respectively) adjusted for confounders (age, sex, T1DM, and T2DM). Stratification by sex demonstrated that carrying the common MC4R rs17782313 is significantly associated with an elevated predisposition to obesity under the recessive model among females only (OR = 1.41, 95% CI: 1.09–1.82, p = 0.01), with an average of 0.85 BMI increment compared with wild type and one risk allele carriers. MC4R rs17782313 significantly interacted with several eating behaviors to enhance the risk of obesity. Our findings demonstrate that MC4R rs17782313 homozygous female carriers are significantly predisposed to obesity amplified by eating behaviors. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
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16 pages, 477 KiB  
Article
Sex Differences in the Efficacy of Mediterranean Diet Treatment: A Nutrigenomics Pilot Study
by Laura Di Renzo, Paola Gualtieri, Giulia Frank, Gemma Lou De Santis, Rossella Cianci, Giulia Bigioni and Antonino De Lorenzo
Genes 2023, 14(11), 1980; https://doi.org/10.3390/genes14111980 - 24 Oct 2023
Cited by 2 | Viewed by 1273
Abstract
The Mediterranean diet (MedD) has been shown to have beneficial effects on health, well-being, and mental status. It potentially modulates gene expressions linked to oxidative stress, contributing to its beneficial effects on overall health. The aim of this study was to assess the [...] Read more.
The Mediterranean diet (MedD) has been shown to have beneficial effects on health, well-being, and mental status. It potentially modulates gene expressions linked to oxidative stress, contributing to its beneficial effects on overall health. The aim of this study was to assess the effects of MedD treatment in healthy human volunteers on the expression of ten genes related to oxidative stress and inflammation in women and men. Of 30 enrolled subjects, 17 were eligible, 10 women and 7 men. All of them received the same MedD treatment. Before and after 8 weeks of MedD treatment, an evaluation of body composition, blood tests, and anthropometric and clinical parameters was performed. Furthermore, 10 genes were amplified and analyzed. The study showed significant differences between females and males in body composition and biochemical parameters before and after MedD treatment. Significant differences between females and males in Resistance Force (p < 0.009) and Diastolic Blood Pressure (p < 0.04) before MedD treatment, and in High-Density Lipoprotein (p < 0.02) after MedD treatment, were observed. Moreover, a significant upregulation of Apolipoprotein E and Angiotensin I-Converting Enzyme in females has been shown. Sex differences impact MedD treatment response, and influence the genetic expression of genes related to oxidative stress; our findings may help to personalize diet therapy and contribute to overall health and well-being. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
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16 pages, 972 KiB  
Article
Antioxidant-Enriched Diet on Oxidative Stress and Inflammation Gene Expression: A Randomized Controlled Trial
by Paola Gualtieri, Marco Marchetti, Giulia Frank, Antonella Smeriglio, Domenico Trombetta, Carmela Colica, Rossella Cianci, Antonino De Lorenzo and Laura Di Renzo
Genes 2023, 14(1), 206; https://doi.org/10.3390/genes14010206 - 13 Jan 2023
Cited by 4 | Viewed by 2512
Abstract
The Mediterranean Diet (MedDiet) is associated with beneficial effects against chronic non-communicable diseases (CNCDs). In particular, the content of micronutrients leads to an improvement of the oxidative and inflammatory profiles. A randomized, parallel, controlled study, on 24 subjects, was conducted to evaluate if [...] Read more.
The Mediterranean Diet (MedDiet) is associated with beneficial effects against chronic non-communicable diseases (CNCDs). In particular, the content of micronutrients leads to an improvement of the oxidative and inflammatory profiles. A randomized, parallel, controlled study, on 24 subjects, was conducted to evaluate if 2-week supplementation with a mixed apple and bergamot juice (MAB juice), had a positive impact on the body composition, the biochemical profile, and oxidative and inflammatory gene expression (Superoxide dismutase (SOD1), Peroxisome Proliferator-Activated Receptor γ (PPARγ), catalase (CAT), chemokine C-C motif ligand 5 (CCL5), Nuclear Factor Kappa B Subunit 1 (NFKB1), Vitamin D Receptor (VDR), and Macrophage Migration Inhibitory Factor (MIF)), respect to a MedDiet. Body composition evaluation analysis showed a gain in lean mass (p < 0.01). Moreover, a significant reduction in total cholesterol/HDL index (p < 0.01) was pointed out between the two groups. Gene expression analysis highlighted an increase in MIF (p ≤ 0.05), PPARγ (p < 0.001), SOD1 (p ≤ 0.05), and VDR (p ≤ 0.05) expressions when comparing MedDiet and MedDiet + MAB juice groups. These data based on the nutrigenomics approach demonstrated that supplementing 2 weeks of MAB juice to the MedDiet could contribute to a reduction in the risk of CNCDs. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
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17 pages, 424 KiB  
Article
Identification and Association of Single Nucleotide Polymorphisms of the FTO Gene with Indicators of Overweight and Obesity in a Young Mexican Population
by Alonso Chama-Avilés, Karla Lucero Flores-Viveros, Jorge Alberto Cabrera-Ayala, Adriana Aguilar-Galarza, Willebaldo García-Muñoz, Lorenza Haddad-Talancón, Ma. de Lourdes Anzures-Cortés, Claudia Velázquez-Sánchez, Jorge Luis Chávez-Servín, Miriam Aracely Anaya-Loyola, Teresa García-Gasca, Víctor Manuel Rodríguez-García and Ulisses Moreno-Celis
Genes 2023, 14(1), 159; https://doi.org/10.3390/genes14010159 - 06 Jan 2023
Cited by 2 | Viewed by 1995
Abstract
(1) Background: obesity is a global public health problem; various factors have been associated with this disease, and genetic factors play a very important role. Previous studies in multiple populations have associated a gene with fat mass and obesity (FTO). Thus, [...] Read more.
(1) Background: obesity is a global public health problem; various factors have been associated with this disease, and genetic factors play a very important role. Previous studies in multiple populations have associated a gene with fat mass and obesity (FTO). Thus, the present work aims to identify and determine associations between genetic variants of FTO with indicators of overweight and obesity in the Mexican population. (2) Methods: a total of 638 subjects were evaluated to compile data on body mass index (BMI), the percentage of body fat (%BF), the waist circumference (WC), the serum levels of triglycerides (TG), and food consumption. A total of 175 genetic variants in the FTO gene were sampled by a microarray in the evaluated population, followed by association statistical analyses and comparisons of means. (3) Results: a total of 34 genetic variants were associated with any of the 6 indicators of overweight and obesity, but only 15 showed mean differences using the recessive model after the Bonferroni correction. The present study shows a wide evaluation of FTO genetic variants associated with a classic indicator of overweight and obesity, which highlights the importance of genetic analyses in the study of obesity. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
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7 pages, 259 KiB  
Article
Congenital Heart Diseases: Genetic Risk Variants and Their Methylation Status
by Melissa Calzada-Dávila, Geovana Calvo-Anguiano, Laura E. Martínez-de-Villarreal, José J. Lugo-Trampe, Sandra M. González-Peña, Patricia R. Ancer-Rodríguez, María D. Hernández-Almaguer and Luis D. Campos-Acevedo
Genes 2022, 13(11), 2115; https://doi.org/10.3390/genes13112115 - 15 Nov 2022
Viewed by 1394
Abstract
(1) Background: The interaction between single nucleotide variants (SNVs) associated with congenital heart diseases (CHDs) and their gene methylation status has not been well researched. The aim of the present study was to determine if there is a relationship between the methy lation [...] Read more.
(1) Background: The interaction between single nucleotide variants (SNVs) associated with congenital heart diseases (CHDs) and their gene methylation status has not been well researched. The aim of the present study was to determine if there is a relationship between the methy lation status (MS) of genes and the allelic variants associated with CHDs. (2) Methods: Seven SNVs of the genes AXIN1, TBX1, TBX20, and MTHFR were selected from the literature. DNA extraction, genotyping, and a methylation analysis were performed on healthy subjects and subjects with CHDs. (3) Results: Twenty-two subjects with CHDs were selected as the case group (15 with ventricular septal defects (VSDs) and 7 with atrial septal defects (ASDs)), and 44 healthy subjects comprised the control group. The MTHFR and AXIN1 genes were hypermethylated in the control group when compared to the case group. When analyzed separately, those with atrial septum defects exhibited greater methylation, except for the gene MTHFR where there were no differences. Only the alternate alleles of MTHFR showed a significantly different methylation status in those without cardiopathy. (4) Conclusions: The MTHFR and AXIN genes were hypermethylated in the control group; however, only the alternate alleles of MTHFR (rs1801133 and rs1801131) showed a significantly different methylation status. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
12 pages, 1208 KiB  
Article
Comprehensive miRNA and DNA Microarray Analyses Reveal the Response of Hepatic miR-203 and Its Target Gene to Protein Malnutrition in Rats
by Kaoru Takahashi, Huijuan Jia, Shoko Takahashi and Hisanori Kato
Genes 2022, 13(1), 75; https://doi.org/10.3390/genes13010075 - 28 Dec 2021
Cited by 2 | Viewed by 1595
Abstract
Adequate protein nutrition is essential for good health. Effects of protein malnutrition in animals have been widely studied at the mRNA level with the development of DNA microarray technology. Although microRNAs (miRNAs) have attracted attention for their function in regulating gene expression and [...] Read more.
Adequate protein nutrition is essential for good health. Effects of protein malnutrition in animals have been widely studied at the mRNA level with the development of DNA microarray technology. Although microRNAs (miRNAs) have attracted attention for their function in regulating gene expression and have been studied in several disciplines, fewer studies have clarified the effects of protein malnutrition on miRNA alterations. The present study aimed to elucidate the relationship between protein malnutrition and miRNAs. Six-week old Wistar male rats were fed a control diet (20% casein) or a low-protein diet (5% casein) for two weeks, and their livers were subjected to both DNA microarray and miRNA array analysis. miR-203 was downregulated and its putative target Hadhb (hydroxyacyl-CoA dehydrogenase β subunit), known to regulate β-oxidation of fatty acids, was upregulated by the low-protein diet. In an in vitro experiment, miR-203 or its inhibitor were transfected in HepG2 cells, and the pattern of Hadhb expression was opposite to that of miR-203 expression. In addition, to clarifying the hepatic miRNA profile in response to protein malnutrition, these results showed that a low-protein diet increased Hadhb expression through downregulation of miR-203 and induced β-oxidation of fatty acids. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
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13 pages, 604 KiB  
Article
Years of Schooling Could Reduce Epigenetic Aging: A Study of a Mexican Cohort
by Juan Carlos Gomez-Verjan, Marcelino Esparza-Aguilar, Verónica Martín-Martín, Cecilia Salazar-Perez, Cinthya Cadena-Trejo, Luis Miguel Gutierrez-Robledo, José Jaime Martínez-Magaña, Humberto Nicolini and Pedro Arroyo
Genes 2021, 12(9), 1408; https://doi.org/10.3390/genes12091408 - 13 Sep 2021
Cited by 5 | Viewed by 2356
Abstract
Adverse conditions in early life, including environmental, biological and social influences, are risk factors for ill-health during aging and the onset of age-related disorders. In this context, the recent field of social epigenetics offers a valuable method for establishing the relationships among them [...] Read more.
Adverse conditions in early life, including environmental, biological and social influences, are risk factors for ill-health during aging and the onset of age-related disorders. In this context, the recent field of social epigenetics offers a valuable method for establishing the relationships among them However, current clinical studies on environmental changes and lifespan disorders are limited. In this sense, the Tlaltizapan (Mexico) cohort, who 52 years ago was exposed to infant malnutrition, low income and poor hygiene conditions, represents a vital source for exploring such factors. Therefore, in the present study, 52 years later, we aimed to explore differences in clinical/biochemical/anthropometric and epigenetic (DNA methylation) variables between individuals from such a cohort, in comparison with an urban-raised sample. Interestingly, only cholesterol levels showed significant differences between the cohorts. On the other hand, individuals from the Tlaltizapan cohort with more years of schooling had a lower epigenetic age in the Horvath (p-value = 0.0225) and PhenoAge (p-value = 0.0353) clocks, compared to those with lower-level schooling. Our analysis indicates 12 differentially methylated sites associated with the PI3-Akt signaling pathway and galactose metabolism in individuals with different durations of schooling. In conclusion, our results suggest that longer durations of schooling could promote DNA methylation changes that may reduce epigenetic age; nevertheless, further studies are needed. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
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Review

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14 pages, 481 KiB  
Review
The Nutriepigenome
by Mario G. Mirisola
Genes 2023, 14(11), 1997; https://doi.org/10.3390/genes14111997 - 25 Oct 2023
Cited by 1 | Viewed by 1095
Abstract
Unlike genetic changes, epigenetics modulates gene expression without stable modification of the genome. Even though all cells, including sperm and egg, have an epigenome pattern, most of these modifications occur during lifetime and interestingly, some of them, are reversible. Lifestyle and especially nutrients [...] Read more.
Unlike genetic changes, epigenetics modulates gene expression without stable modification of the genome. Even though all cells, including sperm and egg, have an epigenome pattern, most of these modifications occur during lifetime and interestingly, some of them, are reversible. Lifestyle and especially nutrients as well as diet regimens are presently gaining importance due to their ability to affect the epigenome. On the other hand, since the epigenome profoundly affects gene expression profile it can be speculated that the epigenome could modulate individual response to nutrients. Recent years have thus seen growing interest on nutrients, macronutrients ratio and diet regimens capable to affect the epigenetic pattern. In fact, while genetic alterations are mostly detrimental at the individual level, reshaping the epigenome may be a feasible strategy to positively counteract the detrimental effect of aging. Here, I review nutrient consumption and diet regimens as a possible strategy to counteract aging-driven epigenome derangement. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
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15 pages, 645 KiB  
Review
Advances and Limitations of Next Generation Sequencing in Animal Diet Analysis
by Gang Liu, Shumiao Zhang, Xinsheng Zhao, Chao Li and Minghao Gong
Genes 2021, 12(12), 1854; https://doi.org/10.3390/genes12121854 - 23 Nov 2021
Cited by 8 | Viewed by 2905
Abstract
Diet analysis is a critical content of animal ecology and the diet analysis methods have been constantly improving and updating. Contrary to traditional methods of high labor intensity and low resolution, the next generation sequencing (NGS) approach has been suggested as a promising [...] Read more.
Diet analysis is a critical content of animal ecology and the diet analysis methods have been constantly improving and updating. Contrary to traditional methods of high labor intensity and low resolution, the next generation sequencing (NGS) approach has been suggested as a promising tool for dietary studies, which greatly improves the efficiency and broadens the application range. Here we present a framework of adopting NGS and DNA metabarcoding into diet analysis, and discuss the application in aspects of prey taxa composition and structure, intra-specific and inter-specific trophic links, and the effects of animal feeding on environmental changes. Yet, the generation of NGS-based diet data and subsequent analyses and interpretations are still challenging with several factors, making it possible still not as widely used as might be expected. We suggest that NGS-based diet methods must be furthered, analytical pipelines should be developed. More application perspectives, including nutrient geometry, metagenomics and nutrigenomics, need to be incorporated to encourage more ecologists to infer novel insights on they work. Full article
(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)
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