Tseng Yu-Yao
Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih Chien University, Taipei, Taiwan.
Nutr Metab (Lond). 2024 Aug 9;21(1):65. doi: 10.1186/s12986-024-00840-w.
Obesity is a global health concern associated with increased risk of diseases like cardiovascular conditions including ischemic heart disease, a leading cause of mortality. The ketogenic diet (KD) has potential therapeutic applications in managing obesity and related disorders. However, the intricate effects of KD on diverse physiological conditions remain incompletely understood. The PI3K-Akt signaling pathway is critical for heart health, and its dysregulation implicates numerous cardiac diseases.
We developed comprehensive mathematical models of the PI3K-Akt signaling pathway under high-fat diet (HFD) and KD conditions to elucidate their differential impacts and quantify apoptosis. Simulations and sensitivity analysis were performed.
Simulations demonstrate that KD can reduce the activation of key molecules like Erk and Trp53 to mitigate apoptosis compared to HFD. Findings align with experimental data, highlighting the potential cardiac benefits of KD. Sensitivity analysis identifies regulators like Trp53 and Bcl2l1 that critically influence apoptosis under HFD.
Mathematical modeling provides quantitative insights into the contrasting effects of HFD and KD on cardiac PI3K-Akt signaling and apoptosis. Findings have implications for precision nutrition and developing novel therapeutic strategies to address obesity-related cardiovascular diseases.
肥胖是一个全球性的健康问题，与包括缺血性心脏病在内的心血管疾病风险增加相关，缺血性心脏病是主要的死亡原因。生酮饮食（KD）在管理肥胖及相关疾病方面具有潜在的治疗应用。然而，KD对多种生理状况的复杂影响仍未完全了解。PI3K-Akt信号通路对心脏健康至关重要，其失调与多种心脏疾病有关。
我们建立了高脂饮食（HFD）和KD条件下PI3K-Akt信号通路的综合数学模型，以阐明它们的不同影响并量化细胞凋亡。进行了模拟和敏感性分析。
模拟表明，与HFD相比，KD可以降低Erk和Trp53等关键分子的激活，从而减轻细胞凋亡。研究结果与实验数据一致，突出了KD对心脏的潜在益处。敏感性分析确定了在HFD下对细胞凋亡有关键影响的调节因子，如Trp53和Bcl2l1。
数学建模为HFD和KD对心脏PI3K-Akt信号传导和细胞凋亡的对比效应提供了定量见解。研究结果对精准营养以及开发解决肥胖相关心血管疾病的新治疗策略具有启示意义。
