Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551039
Pertenecen a esta colección Tesis y Trabajos de grado de las Maestrías correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- Consequences of obesity on one-carbon metabolism across different study models: in silico transcriptomic analyses(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-06-26) Cantú Ruiz, Jesús Daniel; Díaz de la Garza, Rocío Isabel; emipsanchez; Treviño Alvarado, Víctor Manuel; García Ramírez, Noemí; Guéant Rodríguez, Rosa María; School of Engineering and Sciences; Campus Monterrey; Castaño Moreno, Erika YanethObesity is a complex, multifactorial disorder marked by profound disruptions in energy homeostasis and nutrient handling. One-carbon metabolism (1-CM) – the network that fuels cellular methylation and nucleotide biosynthesis – is particularly vulnerable in obesity; individuals with a body mass index (BMI) > 30 kg/m² consistently exhibit reduced circulating levels of key 1-CM micronutrients, yet the underlying regulatory mechanisms remain poorly understood. In this study, 1‑CM gene expression was characterized across three complementary models: (i) adipose and skeletal muscle samples from post‑mortem donors in the GTEx cohort; (ii) white and brown adipose tissue from mice subjected to a high‑fat diet; and (iii) primary adipocytes isolated from human and mouse specimens. A comprehensive list of 1–CM–related genes, curated through UniProt annotation and a targeted literature review, was overlaid onto differential expression results obtained using both the limma and DESeq2 pipelines. Genes with an adjusted p-value < 0.05 were deemed significant. In the GTEx study of 42 tissues analyzed, subcutaneous, visceral adipose, and skeletal muscle (gastrocnemius) tissues were significantly compromised. In these three tissues, a downregulation of folate cycle genes (MTHFD1/2, SHMT2, ALDH1L1) and vitamin B12-processing enzymes (MMACHC, MTRR) was observed. Subcutaneous and visceral adipose tissues showed reduced expression of FOLR1, SLC25A32, and purine biosynthesis genes (GART, ATIC). Skeletal muscle exhibited partial compensatory upregulation (DHFR, ALDH1L1). In the animal model, the differentially expressed genes (DEGs) revealed the upregulation of de novo purine synthesis genes (Atic and Gart), DNA methylation (Dnmt3a, Dnmt3b, and Dnmt1), and folate uptake (Folr1 and Folr2). Folate species interconversion genes, including Mthfr and Aldh1l1, were downregulated. In primary human adipocytes, 41 1-CM genes were differentially expressed (28 upregulated, 13 downregulated; log₂FC range: –4.33 to +4.15). GLDC (–4.33), MTHFD2 (–3.20), MTHFD1L (–1.65), and DNMT1 (–2.90) were markedly suppressed. Conversely, SARDH (+4.10), LRP2 (+4.15), and SHMT1, as well as BHMT2 and ALDH1L1, were upregulated. Folate and B12 transporters (TCN2, SLC19A1, FOLR2) were also elevated.
- Computational identification of genetic polymorphisms influencing human gene expression in obesity gene(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2024-05) Jácome Velasco, Farid; Treviño Alvarado, Víctor Manuel; emimmayorquin; Campus Estado de MéxicoThe heritability of obesity has been estimated to be between 40% and 70%. 60 GWAS and more than 1,100 loci were reported. Most of these loci are in non-coding regions, making it more difficult to understand the role of these variants in the disease. One of the methods to understand these non-coding variants is to estimate their effects on gene expression levels of the neighbouring gene (cis-eQTL) or far away genes (trans-eQTL). This is achieved by a regression model explaining the gene expression level by the genetic variant and other covariates. The GTEx project characterized genetic effects on transcriptome across different tissues with eQTLs but did not report any eQTL on the principally expressed tissue of genes involved in obesity. Our project employed a rigorous eQTL mapping approach, utilizing gene expression and whole genome data from the reputable GTEx database. The genotype data, obtained from the GTEx consortium, was meticulously divided by each of the 22 chromosomes. The expression data, downloaded from the GTEx portal, was carefully processed into an expression matrix. Covariates were included to adjust for principal components, sex, PEER factors and protocol. The MatrixeQTL model, a well-established method, was used for the eQTL mapping of 21 genes related to the leptin-melanocortin pathway in tissues where these genes are highly expressed (pituitary gland, hypothalamus, and adipose visceral tissue). Our thorough approach led to the identification of 8221 eQTLs, with the gene POMC having the most eQTLs. This project generated a set of cis—and trans-eQTLs. These eQTLs may explain the variability of gene expression in genes related to obesity. They can be used for follow-up analyses, including colocalization or Mendelian randomization, to highlight the effect of these variants directly on the obesity phenotype.