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.
- PEGylation of Silk Fibroin Nanoparticles for the Encapsulation of 3,3’-diindolylmethane in Route for the Treatment of Obesity(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025) Escobar Fernández, Aleyda Margarita; Mayolo Deloisa, Karla Patricia; emimmayorquin; Lozano García, Omar; Benavides Lozano, Jorge Alejandro; Morales Martínez, Adriana; School of Engineering and Sciences; Campus Monterrey; Sánchez Trasviña, CalefObesity is responsible for 5 million deaths each year. Considering the complexity of the disease, alternative plant-based compounds, like 3,3´-diindolylmethane (DIM), have become of therapeutical interest. To overcome the poor bioavailability of DIM and enhance its delivery, silk fibroin nanoparticles (SFNP) can be employed. The aim of this work was to PEGylate DIM-loaded SFNP using 5 kDa p-nitrophenyl carbonate methoxy polyethylene glycol (mPEG-PNC), to reduce the previously reported cytotoxicity of SFNP. First, the optimal PEGylation conditions were determined by chromatographic, electrophoretic and computational methods. Silk fibroin (SF) showed higher flexibility, group availability and reactivity when using sodium borate buffer at pH 9.4, thus PEGylation was enhanced. These findings were applied on the PEGylation of SF and SFNP at different mass ratios with mPEG-PNC. After this analysis, PEGylation of DIM-loaded SFNP was performed under a mPEG:SFNP mass ratio of 6:1, achieving a PEGylation efficiency of 11.9 ± 7.79 %. These particles had a spherical shape with a size of 98.98 ± 1.97 nm, a surface charge of -30.86 ± 1.09 mV, and a polydispersity index of 0.18. The encapsulation efficiency of DIM in SFNP was 13.16 ± 4.74%, exceeding previous reports. Drug release analysis in physiological conditions suggests that PEGylation prolongued DIM liberation, even after 48 h. Finally, it was confirmed that PEGylated SFNP reduced cytotoxicity on 3T3-L1 preadipocytes, maintaining a 100% cell viability at all evaluated doses, unlike unmodified SFNP. These results demonstrate that PEGylated SFNP, under the developed methodology, can become a promising vehicle to enhance the delivery of DIM, for the treatment of obesity.
- Evaluation of the biological activity of wounding stress-treated carrots on the development of obesity and associated metabolic disorders(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2024-12-11) Castorena Ramírez, Mariana Denise; Jacobo Velázquez, Daniel Alberto; emimmayorquin; Chuck Hernández, Cristina Elizabeth; Licona Cassani, Cuauhtémoc; School of Engineering and Sciences; Campus Monterrey; Rabadán Chávez, Griselda MericiaAdipose tissue is a complex multicellular organ that serves as both an energy reservoir and an endocrine organ responsible for maintaining energy homeostasis through a set of integrated endocrine and metabolic responses. By storing and mobilizing energy as needed, adipose tissue supports metabolic balance. Similarly, the gut microbiota—a complex intestinal microbial ecosystem—plays a critical role in metabolic health, impacting obesity through lipid metabolism, energy extraction, and inflammation modulation. Postharvest wounding stress, a type of abiotic stress induced by cutting followed by a storage period, has been shown to significantly increase the total phenolic content in carrots, particularly chlorogenic acid (CHA). Given the antioxidant, anti-inflammatory, and anti-obesogenic effects of this dietary phytochemical, this study aimed to evaluate the effect of consuming carrots treated with wounding stress on diet-induced obesity (DIO) and associated metabolic disorders in rats. Male Wistar rats were fed a standard (SD) or hypercaloric diet (HD) supplemented with wounding stress-treated carrots (wsC) or nonstressed carrots (nsC) for 8 weeks. In HD-fed rats, daily consumption of 5 g of wsC (HDwsC) led to a significant decrease in body weight gain (18%) and total white adipose tissue (WAT) accumulation (9.7%) without changes in food or energy intake compared to the HD group. HD-wsC supplementation also improved fat mass distribution, with a significant increase in subcutaneous WAT (20%) and a decrease in visceral WAT (17.3%). These shifts in adipose tissue were consistent with improvements in lipid profiles, as the HD-wsC group showed increased HDL-c levels (40%) and reduced triglycerides (39%), total cholesterol (35%), LDL-c (8.3%), and VLDL-c (38.6%). Additionally, HD-wsC improved glucose metabolism, enhancing oral glucose tolerance and insulin sensitivity, as reflected in lowered AUC values (4.3% and 5.2%, respectively, vs. HD group). Microbiota analysis further revealed that HD-wsC partially alleviated gut dysbiosis, preserving microbial diversity, increasing beneficial bacteria like Butyricoccaceae, and reducing pathogenic bacteria such as Rickettsiaceae. These findings suggest that wounding stress treated-carrots may offer an effective dietary intervention for obesity management, acting through modulation of adipose tissue function, lipid profiles, and gut microbiota composition.
- 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.
- Analysis of immune cells in peripheral blood and colostrum from obese mothers in Mexico(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-05-28) Piñeiro Salvador, Raúl; Brunck, Marion; tolmquevedo; Lara-Díaz, Víctor Javier; Licona-Cassani, Cuauhtémoc; Vásquez-Garza, Eduardo; Escuela de Ingeniería y Ciencias; Campus MonterreyBreastfeeding provides newborns not only nutritional short-term nutrient supply, but also long-term benefits in neural, metabolic, and immune development. Several bioactive components of human milk mediate these long-term benefits over immunity, including living bacteria and leukocytes, or even some modulators like cytokines and antibodies. The immunological properties of milk change over lactation progress and the colostrum (stage of lactation produced within 2 days after birth) is the stage with the highest concentration of these factors. Other factors like maternal health status, genetics or daily variations also influence on milk composition. In this scenario, prolactin promotes leukocyte migration to mammary glands and milk. However, the role of chronic conditions on human milk immune composition like obesity is poorly studied. This is especially important in countries with high rates of maternal obesity, like Mexico, where more than two-thirds of adult women suffer any grade of overweight or obesity. Here, we present an extensive flow-cytometry based characterization of leukocyte subpopulations in peripheral blood and colostrum from lean and obese mothers, as well as an analysis of some of their phenotypes. With this data, we aim to better understanding if obesity affects the process of leukocyte migration to human milk, and promotes possible changes on functionality of human milk leukocytes.
- Effect of moderate exercise on skeletal muscle mitochondrial function and dynamics in obese Zucker rats(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020-06) Nieblas León, Bianca Daniela; NIEBLAS LEON, BIANCA DANIELA; 450250; García Ramírez, Noemí; RR, emipsanchez; García Rivas, Gerardo de Jesús; Castorena Torres, Fabiola; Hernández Brenes, Carmen; De la Garza Hernández, Ana Laura Isabel; Escuela de Medicina y Ciencias de la Salud; Campus Monterrey; Altamirano Barrera, JulioObesity and metabolic syndrome are related to a significant reduction in mitochondrial quality. Current evidence suggests that both conditions promote an unbalance between fusion and fission, the main events of mitochondrial dynamics and this is associated with alterations in mitochondrial function, mainly in highly energetic tissues such as skeletal muscle. In the treatment of obesity and metabolic disorders, the various adaptations resulting from moderate-intensity physical exercise stand out, which are considered to be regulated by AMPK. This project aimed to evaluate modifications in gene and protein expression of the main regulators of mitochondrial dynamics and, using confocal microscopy, determine changes in mitochondrial function through the evaluation of membrane potential and distribution changes in the main mitochondrial subpopulations in a murine model of obesity after chronic moderate exercise. 12 weeks old male Zucker obese rats were randomly divided into a sedentary obese group and an exercise obese group (n=4 per group). The exercise consisted of 4 weeks of swimming training for 60min/5days a week. After 48 hours of the last exercise bout, animals were euthanized and both gastrocnemius muscles were isolated. A significant increase in fission was evidenced by changes in phosphorylation of Drp1 and AMPK. Subsarcolemmal mitochondria showed a more organized network in comparison with the sedentary group while there was no change in the intermyofibrillar region. An increase in fission regulated by AMPK might be segregating damaged mitochondria and enhancing its removal while activating mitochondrial biogenesis to ensure restoration of mitochondrial mass by generating a healthier population in the subsarcolemmal region.