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

Abstract

AbstractMetabolic 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. To address this gap, we conducted a rigorous in silico diet intervention study by leveraging organ-resolved sex-specific whole-body models (WBMs) of metabolism. These models were utilized to computationally evaluate the effect of 12 diverse dietary regimens on key MetS biomarkers—glucose, triacylglycerides (TAG), LDL-C, and HDL-C—and fatty acid beta-oxidation in both males and females. Our analyses elucidated molecular mechanisms underlying the link between conventionally unhealthy diets and elevated MetS risk. Specifically, a typical Unhealthy or Keto 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 metabolic profiles, characterized by lower TAG storage and LDL-C to HDL-C ratios. Notably, plant-based (Vegan and Vegetarian) diets induced elevated fatty acid oxidation compared to high-fat regimens, suggesting their potential in mitigating MetS risk. Pronounced gender differences in metabolic responses to diets were also observed in our analyses, highlighting the need for gender-tailored dietary recommendations. Additionally, our study delineated organ-specific contributions to the MetS biomarkers, with the liver and lungs identified as major regulators of blood glucose homeostasis. Overall, this study contributes to a deeper understanding of the intricate interactions between diet and MetS risk.