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.