In this study we used Drosophila melanogaster as a model organism to investigate the relevance of adipose tissue lipolysis as an energy providing process, which determines cardiac function under energy-deprived, catabolic conditions. We analyzed the role of the adipose triglyceride lipase ortholog in D. melanogaster, Brummer (bmm), which is also the key enzyme for fat body lipolysis in flies.

Cardiac function of male flies with fat-body specific RNAi-mediated bmm knockdown (fbbmmKD) was analyzed using high-speed video imaging. Additionally, mass spectrometry-based metabolomic profiling was performed on whole fly lysates. Finally, cellular respiration of ex vivo heart preparations was measured using Seahorse XFe96 Analyzer.

FbbmmKD flies showed normal cardiac parameters when compared to control flies. Challenging flies with starvation for 72 h led to cardiac dysfunction in control flies. Interestingly, starvation-induced cardiac dysfunction was rescued in fbbmmKD flies. Furthermore, fbbmmKD flies had significantly prolonged starvation survival. While cardiac dysfunction was apparently caused by an exhaustion of high-energy substrates during starvation, perturbation of fat body lipolysis led to enlarged TAG energy stores and elevated levels of whole-body energy substrates measured using mass spectrometry. Moreover, hearts from starved fbbmmKD flies had maintained ATP-linked respiration compared to starved control hearts. Resupplying energy substrates to starved control hearts rescued cardiac dysfunction, indicating that exhaustion of high-energy substrates caused cardiac dysfunction.

We suggest that impaired fat body lipolysis led to maintenance of myocardial energy supply thereby protecting against cardiac dysfunction induced by energy depletion. This study shows that inhibition of adipose tissue lipolysis is beneficial during energy depletion with respect to cardiac function and survival.