Abstract
Significant recent evidence suggests that metabolism is intricately linked to the regulation and dysfunction of complex cellular and physiological responses ranging from altered metabolic programs in cancers and aging to circadian rhythms and molecular clocks. While the metabolic pathways and their fundamental control mechanisms are well established, the precise cellular mechanisms underpinning, for example, enzymatic pathway control, substrate preferences or metabolic rates, remain far less certain. Comprehensive, continuous metabolic studies on model organisms, such as the fruit fly Drosophila melanogaster, may provide a critical tool for deciphering these complex physiological responses. Here, we describe the development of a high-resolution calorimeter, which combines sensitive thermometry with optical imaging to concurrently perform measurements of the metabolic rate of ten individual flies, in real-time, with ~100 nW resolution. Using this calorimeter we have measured the mass-specific metabolic rates of flies of different genotypes, ages, and flies fed with different diets. This powerful new approach enables systematic studies of the metabolic regulation related to cellular and physiological function and disease mechanisms.
Highlights
Metabolism is defined as the sum of all physical and biochemical processes in living organisms that either produce or consume energy[1,2]
Our studies demonstrate that our sensitive calorimeter can precisely quantify the metabolic activity of individual Drosophila and will enable further studies investigating metabolic disorders associated with many pathologies including aging, circadian disruption, mitochondrial dysfunction among others
In order to better visualize the relationship between metabolism and activity level, we present in Fig. 2b a plot of the heat output data as a function of fly activity for the same Canton S fly from Fig. 2a
Summary
Metabolism is defined as the sum of all physical and biochemical processes in living organisms that either produce or consume energy[1,2]. A number of techniques, including quantification of metabolites, respirometry and direct calorimetric measurements, have been utilized to characterize the metabolic output and state of biological systems ranging from collections of cells to whole organisms. The first strategy, broadly speaking, is based on profiling (i.e. quantifying the concentrations of) specific, low molecular weight metabolites that, as fundamental constituents of the key biochemical pathways, serve as metabolic indicators[15,16]. This strategy has significant limitations: (1) Destructive sample preparation prevents continuous, time-resolved measurements and (2) relating the detected biomarkers to biological mechanisms remains challenging and uncertain[15]. Our studies demonstrate that our sensitive calorimeter can precisely quantify the metabolic activity of individual Drosophila and will enable further studies investigating metabolic disorders associated with many pathologies including aging, circadian disruption, mitochondrial dysfunction among others
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