The heart is better protected against myocardial infarction in the fed state compared to the fasted state

Abstract

Objective: A variety of calorie restriction diets and fasting regimens are popular among overweight people. However, starvation could result in unexpected cardiovascular effects. Therefore, it is necessary to evaluate the short-term effects of diets on cardiovascular function, energy metabolism and potential risk of heart damage in case of myocardial infarction. The objective of the present study was to investigate whether the increased level of glucose oxidation or reduction of fatty acid (FA) load in the fed state provides the basis for protection against myocardial infarction in an experimental rat model of ischemia-reperfusion.

Materials/methods: We tested the effects of the availability of energy substrates and their metabolites on the heart functionality and energy metabolism under normoxic and ischemia-reperfusion conditions.

Results: In a fasted state, the heart draws energy exclusively from FAs, whereas in a fed state, higher concentration of circulating insulin ensures a partial switch to glucose oxidation, while the load of FA on heart and mitochondria is reduced. Herein, we demonstrate that ischemic damage in hearts isolated from Wistar rats and diabetic Goto-Kakizaki rats is significantly lower in the fed state compared to the fasted state.

Conclusions: Present findings indicate that postprandial or fed-state physiology, which is characterised by insulin-activated glucose and lactate utilisation, is protective against myocardial infarction. Energy metabolism pattern in the heart is determined by insulin signalling and the availability of FAs. Overall, our study suggests that even overnight fasting could provoke and aggravate cardiovascular events and high-risk cardiovascular patients should avoid prolonged fasting periods.

Keywords: AN; AR; ATP; BSA; CPT1A, CPT1B; ETC; FA; FATP1; Fasted; Fatty acids; Fed; GIK; GK; Glucose; Glut1, Glut4; Goto–Kakizaki; HK2; HR; HSL; IS; Insulin; KH; Krebs–Henseleit; LAD; LVDP; P-Akt; PDHx; PDK4; PGC-1α; PPAR-α; ROS; SEM; TG; UCP1, UCP3; adenosine triphosphate; area at risk; area of necrosis; bovine serum albumin; carnitine palmitoyltransferase 1A and 1B; electron transfer chain; fatty acid; fatty acid transport protein 1; glucose transporter 1 and 4; glucose–insulin–potassium; heart rate; hexokinase 2; hormone-sensitive lipase; infarct size; left anterior descending coronary artery; left ventricular developed pressure; peroxisome proliferator-activated receptor alpha; peroxisome proliferator-activated receptor-γ coactivator; phosphorylated Akt; pyruvate dehydrogenase complex, component X; pyruvate dehydrogenase lipoamide kinase isozyme 4; qRT-PCR; quantitative reverse transcriptase polymerase chain reaction; reactive oxygen species; standard error of the mean; triglycerides; uncoupling proteins 1 and 3.