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预期效果。 需要限制和新的治疗方法。PPG的最新结果表明， 碳水化合物/高脂肪饮食可以防止HF的发展和进展。脂肪酸 饮食组成可能对HF的发生和进展有重大影响。进气 多不饱和脂肪酸（PUFA）对心脏基因表达的影响更有利， 线粒体功能和心肌细胞凋亡。我们也 观察到高糖摄入可加速HF的发展和进展。这 项目调查了膳食常量营养素组成对 HF的进展。我们假设：1）高摄入PUFA（18：2n-6和18：3 n-3）或 EPA+DHA）预防和逆转线粒体功能，细胞凋亡， 心肌细胞肥大、纤维化、心室重塑和收缩功能障碍， HF;和2）高糖饮食激活胰岛素刺激的生长和ROS产生， 加速了HF的发展。将在已建立的HF模型中进行研究。 通过使用以下方法在特定途径中进行靶向改变来解决不可理解的机制 营养学、药理学和遗传学方法。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阻止 或与标准高碳水化合物饮食相比逆转HF的进展。 2)确定标准高碳水化合物饮食的膳食补充剂的效果 UJ-3 PUFA（EPA+DHA）对已建立的HF的进展的影响。 3)阐明胰岛素信号在HF患者高糖饮食不良反应中的作用。 4)确定ROS产生在介导高糖不良反应中的作用 HF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.