Optimization of Macronutrient intake in Heart Failure

目前治疗心力衰竭(HF)的药理学方法的益处接近其 限制和新的辅助疗法是必要的。这个PPG的最新结果表明，Low 碳水化合物/高脂肪饮食可能会阻止心力衰竭的发生和发展。脂肪酸 饮食的组成可能对心力衰竭的发展和进展有重大影响。摄入量 多不饱和脂肪酸(PUFA)对心脏基因表达有更有利的作用， 线粒体功能、心肌细胞凋亡率高于高饱和脂肪饮食。我们也 观察到高糖摄入可加速心力衰竭的发生和发展。这 该项目调查了膳食中大量营养素的组成对 心衰的进展。我们假设1)大量摄入多不饱和脂肪酸(18：2n-6和18：3n-3)或 EPA+DHA)可防止和逆转线粒体功能恶化、细胞凋亡、 心肌细胞肥大、纤维化、腔室重构和收缩功能障碍 以及2)高糖饮食激活胰岛素刺激的生长和ROS的产生 加速心力衰竭的进展。研究将在已建立的HF模型中进行。 不衍生的机制是通过在特定的通路中使用 营养、药理和遗传方法。具体目标是： 1)评估由饱和脂肪酸或多不饱和脂肪酸组成的高脂肪饮食停止的能力 或者与标准的高碳水化合物饮食相比，逆转心力衰竭的进程。 2)确定补充标准高碳水化合物饮食的效果 UJ-3PUFA(EPA+DHA)对已建立的心衰进展的影响。 3)阐明胰岛素信号在高糖饮食致心力衰竭不良反应中的作用。 4)确定ROS的产生在调节高糖不良反应中的作用 以HF表示的饮食。

The benefits of current pharmacological approaches to treating heart failure (HF) are near their limits and new adjunctive therapies are needed. Recent results from this PPG suggest that low carbohydrate/high fat diets may prevent the development and progression of HF. The fatty acid composition of the diet may have a major impact on development and progression of HF. Intake of polyunsaturated fatty acids (PUFA) has a more favorable effect on cardiac gene expression, mitochondrial function, and cardiomyocyte apoptosis than a high saturated fat diet. We also observed that high sugar intake may accelerate the development and progression of HF. This Project investigates the mechanistic effects of dietary macronutrient composition on the progression of HF. We hypothesize that 1) high intake of PUFA (18:2n-6 and 18:3n-3) or the EPA+DHA) prevents and reverses deterioration in mitochondrial function, apoptosis, cardiomyocyte hypertrophy, fibrosis, chamber remodeling and contractile dysfunction in HF; and 2) a high sugar diet activates insulin-stimulated growth and ROS production and accelerates the progression of HF. Studies will be performed in established models of HF. Underiying mechanisms are addressed with targeted alterations in specific pathways using nutritional, pharmacological, and genetic approaches. The specific aims are: 1) Assess the ability of high fat diets comprised of saturated fatty acids or PUFA to stop or reverse the progression of HF compared to a standard high carbohydrate diet. 2) Determine the effects of dietary supplementation of a standard high carbohydrate diet with UJ-3PUFA (EPA+DHA) on the progression of established HF. 3) Elucidate the role of insulin signaling in the adverse effects of a high sugar diet in HF. 4) Determine the role of ROS generation in mediating the adverse effects of high sugar diet in HF.