Biology subjects

McCreery, C. V.

Publications and source records attributed to McCreery, C. V..

2 recordsLinked to original sources

bioRxiv2024

Unraveling the Link between Nutrition and Metabolic Syndrome Risk through In Silico Dietary Interventions

BackgroundMetabolic Syndrome (MetS) is a cluster of metabolic disorders that substantially increases the risk of chronic metabolic diseases. Diet is known to play a crucial role in the progression of MetS, yet a mechanistic understanding of its impact on MetS risk remains elusive. MethodsTo address this gap, we conducted a rigorous in silico diet intervention study by leveraging organ-resolved sex-specific whole-body models of metabolism. These models were utilized to computationally evaluate the effect of 12 diverse dietary regimens on key MetS biomarkers--glucose, triacylglycerol (TAG), LDL-C, and HDL-C--and fatty acid beta-oxidation in both males and females. ResultsOur analyses elucidated molecular mechanisms underlying the link between conventionally unhealthy diets and elevated MetS risk. Specifically, a typical Unhealthy diet indicated elevated TAG storage in the adipocytes and increased LDL-C to HDL-C ratios across both genders. Conversely, healthier dietary patterns like the Mediterranean and Vegan diets promoted favorable profiles for these biomarkers. Beyond substantiating these known dietary impacts, our analysis also revealed non-intuitive responses to diet. Notably, plant-based (Vegan and Vegetarian) diets induced elevated fatty acid oxidation compared to high-fat regimens like the Ketogenic diet, suggesting their potential in mitigating MetS risk. Pronounced gender differences in metabolic responses to diets were also observed, highlighting the need for gender-tailored dietary recommendations. Organ-specific dietary responses and their contributions to MetS biomarkers were also delineated, pinpointing the liver and lungs as major regulators of blood glucose homeostasis. ConclusionsThis study contributes to a deeper understanding of the intricate interactions between diet and MetS risk.

systems biology↗

bioRxiv2024

Investigating intestinal epithelium metabolic dysfunction in Celiac Disease using personalized genome scale models

Celiac Disease (CeD) is an autoimmune condition characterized by an aberrant immune response triggered by the ingestion of gluten, which damages epithelial cells lining the small intestine. Small intestinal epithelial cells (sIECs) play a key role in various metabolic processes, including the enzymatic digestion and absorption of nutrients. Although nutritional malabsorption is widely recognized in CeD, the underlying disrupted metabolic processes remain largely undefined. To address this knowledge gap, we constructed personalized gender-specific genome-scale models of sIEC metabolism using transcriptional data from 42 subjects with active CeD, remission CeD, and healthy controls. We computationally simulated these models under a relevant diet for each group of subjects to assess the activity of 59 metabolic tasks essential for sIEC function and to profile metabolite secretion into the bloodstream and intestinal lumen. These investigations revealed significant variations in the activity of 25 metabolic tasks in active and remission CeD models. These tasks impact critical processes integral to sIEC function such as amino acid metabolism, nucleotide synthesis and DNA repair, ATP generation, and oxidative stress regulation. Additionally, we identified 54 metabolites with altered secretion profiles in CeD, encompassing amino acids, vitamins, antioxidants, and fatty acids. Furthermore, we pinpointed 22 FDA-approved drugs that target the genes associated with differentially active metabolic functions whose altered activities adversely affect sIECs in CeD, potentially helping to restore their normal activity. Our study unveils new insights into the metabolic reprogramming of sIECs in CeD, paving the way for therapeutic interventions targeting dysregulated metabolic processes.

systems biology↗