A energy shift from fatty acid to glucose is detrimental to pressure-overloaded heart

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461123
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Gunma University
• Principal Investigator: Iso Tatsuya 群馬大学, 大学院医学系研究科, 准教授 (10400756)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 分子心臓病 / エネルギー代謝 / 脂肪酸 / グルコース / 心不全 / 構造リモデリング / 代謝リモデリング

Outline of Final Research Achievements

Under increased workload, the heart shows structural (cardiac hypertrophy and fibrosis) and metabolic remodeling. Double knockout mice lacking FABP-4 and -5 and CD36 knockout mice exhibit reduced uptake of fatty acid with a robust increase in glucose uptake by metabolic compensation. When hearts were pressure-overloaded by trans-aortic constriction, cardiac contractile dysfunction was markedly exacerbated in both mice. Metabolic analysis revealed that pool size of the TCA cycle, or total energy supply, was significantly reduced despite a further increase in glucose uptake by TAC, leading to a reduction in ATP synthesis. In contrast, de novo synthesis of molecules for cardiac hypertrophy (i.e. amino acids, nucleic acids and fatty acids) was likely to be facilitated despite a reduction in total energy supply. Thus, the heart favors anabolic reactions rather than ATP synthesis during the development of cardiac hypertrophy even under conditions where total energy supply is limited.

Free Research Field

循環器内科学