Fasting as a precursor to high-fat diet enhances mitochondrial resilience in Drosophila melanogaster

Changes in diet type and nutrient availability can impose significant environmental stress on organisms, potentially compromising physiological functions and reproductive success. In nature, dramatic fluctuations in dietary resources are often observed and adjustments to restore cellular homeostasis are crucial to survive this type of stress. In this study, we exposed male Drosophila melanogaster to two modulated dietary treatments: one without a fasting period before exposure to a high-fat diet and the other with a 24-h fasting period. We then investigated mitochondrial metabolism and molecular responses to these treatments. Exposure to a high-fat diet without a preceding fasting period resulted in disrupted mitochondrial respiration, notably at the level of complex I. On the other hand, a short fasting period before the high-fat diet maintained mitochondrial respiration. Generally, transcript abundance of genes associated with mitophagy, heat-shock proteins, mitochondrial biogenesis, and nutrient sensing pathways increased either slightly or significantly following a fasting period and remained stable when flies were subsequently put on a high-fat diet, whereas a drastic decrease of almost all transcript abundances was observed for all these pathways when flies were exposed directly to a high-fat diet. Moreover, mitochondrial enzymatic activities showed less variation after the fasting period than the treatment without a fasting period. Overall, our study sheds light on the mechanistic protective effects of fasting prior to a high-fat diet and highlights the metabolic flexibility of Drosophila mitochondria in response to abrupt dietary changes and have implication for adaptation of species to their changing environment.