Comparative mathematical modeling reveals the differential effects of high-fat diet and ketogenic diet on the PI3K-Akt signaling pathway in heart.

IF 3.9 2区医学 Q2 NUTRITION & DIETETICS

Nutrition & Metabolism Pub Date : 2024-08-09 DOI:10.1186/s12986-024-00840-w

Yu-Yao Tseng

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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数学模型比较揭示了高脂饮食和生酮饮食对心脏 PI3K-Akt 信号通路的不同影响。

背景：肥胖是一个全球关注的健康问题，与心血管疾病（包括缺血性心脏病）等疾病风险增加有关，而缺血性心脏病是导致死亡的主要原因。生酮饮食（KD）在控制肥胖和相关疾病方面具有潜在的治疗用途。然而，人们对生酮饮食对各种生理状况的复杂影响仍然知之甚少。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。研究人员进行了模拟和敏感性分析：模拟结果表明，与高脂饮食相比，KD能减少Erk和Trp53等关键分子的激活，从而缓解细胞凋亡。研究结果与实验数据一致，凸显了KD对心脏的潜在益处。敏感性分析确定了 Trp53 和 Bcl2l1 等调控因子，它们对高频分解下的细胞凋亡有关键影响：结论：数学建模提供了定量洞察力，揭示了 HFD 和 KD 对心脏 PI3K-Akt 信号转导和细胞凋亡的不同影响。研究结果对精准营养和开发新型治疗策略以解决与肥胖相关的心血管疾病具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nutrition & Metabolism 医学-营养学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Nutrition & Metabolism publishes studies with a clear focus on nutrition and metabolism with applications ranging from nutrition needs, exercise physiology, clinical and population studies, as well as the underlying mechanisms in these aspects. The areas of interest for Nutrition & Metabolism encompass studies in molecular nutrition in the context of obesity, diabetes, lipedemias, metabolic syndrome and exercise physiology. Manuscripts related to molecular, cellular and human metabolism, nutrient sensing and nutrient–gene interactions are also in interest, as are submissions that have employed new and innovative strategies like metabolomics/lipidomics or other omic-based biomarkers to predict nutritional status and metabolic diseases. Key areas we wish to encourage submissions from include: -how diet and specific nutrients interact with genes, proteins or metabolites to influence metabolic phenotypes and disease outcomes; -the role of epigenetic factors and the microbiome in the pathogenesis of metabolic diseases and their influence on metabolic responses to diet and food components; -how diet and other environmental factors affect epigenetics and microbiota; the extent to which genetic and nongenetic factors modify personal metabolic responses to diet and food compositions and the mechanisms involved; -how specific biologic networks and nutrient sensing mechanisms attribute to metabolic variability.