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Updated: Feb 6, 2026
Methods for the Determination of Rates of Glucose and Fatty Acid Oxidation in the Isolated Working Rat Heart
Published on: September 28, 2016
Free fatty acid can induce cardiac dysfunction and alter insulin signaling pathways in the heart
Lina Han1, Jiali Liu1, Leilei Zhu1
1Department of endocrinology and metabolism, West China Hospital, Sichuan University, Guoxue lane 37, Chengdu City, Sichuan Province, 610041, People's Republic of China.
Background:
Insulin resistance has been independently related to heart failure. However, the specific mechanisms of high FFA levels in the pathophysiology of heart failure in insulin-resistant states are remain largely unclear. This study investigated whether elevated circulating free fatty acids (FFA) levels result in impaired cardiac structure and function in vivo via insulin-related signaling pathways in myocardium.
Methods:
Male Wistar rats were randomly divided into the intralipid group (20% intralipid plus heparin infusion) and the control group (glycerol infusion). Blood samples were collected before and after 6-, 12-, and 24-h infusions. Cardiac structure and function were measured using echocardiography. Maximum velocity of myocardial contraction (+dP/dt max) and diastole (-dP/dt max) were measured using a physiological polygraph in vivo. Heart tissues were collected for western blotting.
Results:
Compared with the control group, plasma FFA, plasma glucose, and serum insulin levels increased significantly in the intralipid group. With increasing infusion time, cardiac function in the intralipid group decreased gradually compared with the control group. After a 24-h infusion, early (E', cm/s) diastolic peak velocities and (-dP/dt max) decreased significantly. Protein expression of phosphatidylinositol 3-kinase (PI3K), the serine/threonine kinase Akt, and phosphorylated Akt in myocardium increased after a 6-h infusion and decreased significantly after a 24-h infusion in the intralipid group. Protein expression of glucose transporter type 4 (GLUT4), Adenosine 5'-monophosphate -activated protein kinase (AMPK), phosphorylated AMPK(p-AMPK), and endothelial nitric oxide synthase (eNOS) in myocardium gradually decreased in the intralipid group.
Conclusions:
Elevated FFA levels may impair cardiac function and cardiac dysfunction might result from myocardial insulin resistance with significant changes to PI3K-Akt-GLUT4 and AMPK-eNOS signaling pathways with increasing FFA levels.
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