The Circadian Clock Interacts with Metabolic Physiology to Influence Reproductive Fitness

Abstract

Circadian rhythms are regulated by a synchronized system of central and peripheral clocks. Here we show that a clock in the Drosophila fat body drives rhythmic expression of genes involved in metabolism, detoxification, the immune response and steroid hormone regulation. Some of these genes cycle even when the fat body clock is disrupted indicating they are regulated by exogenous factors. Food is an important stimulus as limiting food availability to a six-hour interval each day drives rhythmic expression of genes in the fat body. Restricting food to a time of day when consumption is typically low desynchronizes internal rhythms because it alters the phase of rhythmic gene expression in the fat body without affecting the brain clock. Flies maintained on this paradigm produce fewer eggs than those restricted to food at the normal time. These data suggest that desynchrony of endogenous rhythms, caused by aberrant feeding patterns, affects reproductive fitness.

Circadian and feeding cues integrate to drive rhythms of physiology in Drosophila insulin-producing cells

“…While many tissue-specific transcript rhythms are generated by tissue-autonomous clocks, the clock in the fat body does not drive the cycling of all circadian fat body genes (Xu et al 2011); rhythmic expression of several transcripts is regulated by clocks in other tissues, such as in NPF/ NPY neurons (Erion et al 2016). In this study, we found that another neuropeptide signal from the brain regulates rhythmic expression of a different fat body gene (sxe2) (Fig.…”

“…S1). sxe2 transcript rhythms dampened in DD under ad lib conditions, as is typical for cyclically expressed fat body genes (Xu et al 2011), and restricted feeding did not restore a rhythm (Fig. 2E).…”

“…Previous work in our laboratory identified food-entrainable genes in the fat body, some of which are food-entrainable only in the absence of a functional clock, and some of which are food-entrainable through the clock (Xu et al 2011). To test whether sxe2 is a food-entrainable gene, we kept both wild-type and per 01 flies in DD either with ad lib food or under restricted feeding conditions, with food supplied only from CT 9-15, a time when wild-type flies normally have low food intake (Supplemental Fig.…”

“…The fat body contains a molecular clock that functions together with the brain clock to maintain metabolic homeostasis (Xu et al 2008). The expression of many genes cycles in the fat body, and ∼20% of these maintain their rhythmicity in the absence of the fat body clock, with cycling of some driven by the central brain clock through the neuropeptide F (NPF)/NPY system (Xu et al 2011;Erion et al 2016) However, several fat body transcripts are not modulated by the NPF system in Drosophila but by other, still unidentified clock inputs from other tissues.…”

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

“…It is not clear however if the changes in these genes have a direct influence on the increase in cold tolerance or if changes of the expression levels of these genes affect changes to the circadian rhythms of the fly in anticipation of the change in seasonal photoperiod. Further functional genetic studies will allow disentanglement of these hypothesis but given extensive work showing how the clock genes have a large influence on the regulation of metabolic processes in Drosophila (Xu et al, 2008;Xu et al, 2011;Sahar and SassoneCorsi, 2012) we suggest that clock genes are good candidates for orchestrating the shifts in metabolic profile seen during cold acclimation.…”