Abstract
Fatty acid constitutes a major energy substrate in the heart to fuel contraction under aerobic conditions. Ischemia downregulates fatty acid metabolism to adapt to the limited oxygen supply and makes glucose the preferred substrate. However, the mechanism of the myocardial metabolic shift during ischemia remains unknown. Here, we show that cardiomyocyte secretion of lipoprotein lipase (LPL), a principal enzyme that converts triglycerides to free fatty acids and glycerol, increased during myocardial infarction (MI). Cardiomyocyte-specific LPL deficiency enhanced cardiac dysfunction and apoptosis following MI. Deficiency of aquaporin 7 (AQP7), a glycerol channel in cardiomyocytes, increased the myocardial infarct size and apoptosis in response to ischemia. Ischemic conditions activated glycerol-3-phosphate dehydrogenase 2 (GPD2), which converts glycerol-3-phosphate into dihydroxyacetone phosphate to facilitate ATP synthesis from glycerol. Conversely, GPD2 deficiency exacerbated cardiac dysfunction after acute MI. Together, these results identify that LPL/AQP7/GPD2-mediated glycerol metabolism plays an important role to bridge glucose and lipid metabolism in MI and prevent myocardial ischemia-related damage.
LPL/AQP7/GPD2 promotes glycerol metabolism under hypoxia and prevents cardiac dysfunction during ischemia
