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Fumarate is a Krebs cycle intermediate involved in energy generation. However, metabolites can also act as signalling molecules, regulating cell function. Here we identify novel intracrine and paracrine signalling roles for fumarate.In-depth metabolomics screening showed that perfused rat hearts exposed to acute hypoxia increased intracellular fumarate concentrations by 3.3-fold. Elevating fumarate in human iPSC-derived cardiomyocytes reprogrammed cardiac metabolism, decreasing fatty acid oxidation and increasing glycolysis as evidenced by bulk RNAseq and metabolic flux measurements using radioactive isotopes. Fumarate also reshaped mitochondrial network morphology, detected using confocal microscopy, and decreased mitochondrial respiration assessed using a Seahorse analyser. Transcriptomics identified non-metabolic pathways regulated by fumarate, including circadian rhythms, ion transport and signalling by GPCR. In response to chronic hypoxia, fumarate release from the cell was increased by 71%, independent of changes in membrane integrity, and could be decreased by inhibiting monocarboxylate transporters. Finally, FRET experiments and in silico modelling showed that extracellular fumarate acutely activates sarcolemmal Gi-coupled pathways, decreasing cAMP levels.In conclusion, fumarate selectively accumulates under hypoxia, acting both intracellularly as a signalling molecule regulating metabolism and extracellularly as a paracrine signal via G-protein-coupled receptors, reprogramming neighbouring cells.