The Circadian Clock, Light, and Cryptochrome Regulate Feeding and Metabolism in Drosophila

Abstract

Recent studies in mammals have demonstrated a central role for the circadian clock in maintaining metabolic homeostasis. In spite of these advances, however, little is known about how these complex pathways are coordinated. Here, we show that fundamental aspects of the circadian control of metabolism are conserved in the fruit fly Drosophila. We assay feeding behavior and basic metabolite levels in individual flies and show that, like mammals, Drosophila display a rapid increase in circulating sugar following a meal, which is subsequently stored in the form of glycogen. These daily rhythms in carbohydrate levels are disrupted in clock mutants, demonstrating a critical role for the circadian clock in the postprandial response to feeding. We also show that basic metabolite levels are coordinated in a clock-dependent manner and that clock function is required to maintain lipid homeostasis. By examining feeding behavior, we show that flies feed primarily during the first 4 hours of the day and that light suppresses a late day feeding bout through the cryptochrome photoreceptor. These studies demonstrate that central aspects of feeding and metabolism are dependent on the circadian clock in Drosophila. Our work also uncovers novel roles for light and cryptochrome on both feeding behavior and metabolism.

Dietary Restriction Extends the Lifespan of Circadian Mutants tim and per

“…We then measured lipid storage levels using thin-layer chromatography (Ulgherait et al, 2014). In agreement with published data (Allen et al, 2016; Katewa et al, 2016; Seay and Thummel, 2011), per 01 females exhibited lower levels of lipid storage than controls (Figure S1G). Further supporting altered lipid metabolism, we also found that during starvation per 01 mutants lost lipid stores more rapidly than controls (Figure S1G).…”

Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila

“…Genome-wide circadian expression profiling studies have uncovered potential connections between circadian clocks and many aspects of metabolism, including energy, carbohydrate, amino acid, lipid, and protein metabolism, as well as detoxification (Beaver et al, 2012; Panda and Hogenesch, 2004; Wijnen and Young, 2006). In flies, recent studies have highlighted the regulation of lipid and carbohydrate metabolism by circadian clocks (DiAngelo et al, 2011; Seay and Thummel, 2011; Xu et al, 2011). Although the levels of total TGs do not show circadian rhythmicity, flies mutant for circadian genes as such tim ( tim 01 ) and cry ( cry 01 ) show reduction in total levels of TGs (Seay and Thummel, 2011).…”

Methods for studying metabolism in Drosophila

“…Labeled animals are transferred to unlabeled food for several hours to allow them to clear radioactivity that is nonspecifically bound to the cuticle. They are then subjected to Cerenkov counting in a scintillation counter to quantify food uptake [27, 28]. Scintillation fluid can be used if the animals are sacrificed and lower levels of radiation are employed in the diet.…”