Abstract 12815: Physiological Cardiac Hypertrophy is Evoked by Markedly Increased Glucose Consumption and Insulin Signaling in Mice Lacking Both Fatty Acid Binding Protein4 and -5
Endothelial cells (EC) of muscle-type continuous capillary act as functional interface between blood plasma and tissue fluid. Fatty acids (FA) are major energy substrates in various organs including heart. FA binding proteins (FABPs) are cytosolic FA chaperones that regulate cellular and systemic metabolism of lipids. We have provided evidence for a novel function of FABP4 (aP2) and FABP5 (mal1) as endothelial FA carriers between microvessels and interstitial fluid functioning in trans-endothelial FA transport. Both FABP4/5 were abundantly expressed in EC of muscle-type continuous capillary. Mice deficient for both FABP4/5 (FABP4/5 DKO mice) exhibited defective trans-endothelial FA transport in FA-metabolizing organs including heart with compensatory and dramatic up-regulation of glucose consumption in heart. Here we report that the DKO mice show enhanced insulin signaling and physiological hypertrophy in the hearts. Although insulin signal transduction estimated by phosphorylation of insulin receptor-β (IR-β) and Akt was equivalent without insulin treatment, the phosphorylation level induced by insulin was significantly higher in the DKO than the wild type mice. Along with the finding that uptake of 18F-FDG, glucose analogue, in the heart of the DKO mice was remarkably higher without insulin treatment under fasting condition, increased glucose consumption in the heart of the DKO mice during fasting is likely to be independent of insulin signal transduction. Apart from independence of insulin signaling in glucose consumption during fasting, insulin signal transduction by insulin treatment was more sensitive in the DKO mice. We next studied difference of characteristics of the hearts by enhanced glucose metabolism. Heart weight (HW) and HW/body weight (BW) ratio were significantly higher in the DKO mice than the wild type (HW; 109.2 ± 3.2 vs. 116.7 ± 7.7 mg, HW/BW; 4.28 ± 0.14 vs. 4.68 ± 0.06 mg/g, p<0.05). There was no significant difference in blood pressure, heart rate, cardiac contraction, fibrosis and expression of several markers for cardiac overload such as ANP and BNP. These findings suggest that markedly increased glucose consumption and/or resultant enhancement of insulin signal transduction can cause physiological hypertrophy.
- © 2011 by American Heart Association, Inc.