title: Circadian and feeding cues integrate to drive rhythms of physiology in Drosophila insulin-producing cells.
abstract: Circadian clocks regulate much of behavior and physiology, but the mechanisms by which they do so remain poorly understood. While cyclic gene expression is thought to underlie metabolic rhythms, little is known about cycles in cellular physiology. We found that Drosophila insulin-producing cells (IPCs), which are located in the pars intercerebralis and lack an autonomous circadian clock, are functionally connected to the central circadian clock circuit via DN1 neurons. Insulin mediates circadian output by regulating the rhythmic expression of a metabolic gene (sxe2) in the fat body. Patch clamp electrophysiology reveals that IPCs display circadian clock-regulated daily rhythms in firing event frequency and bursting proportion under light:dark conditions. The activity of IPCs and the rhythmic expression of sxe2 are additionally regulated by feeding, as demonstrated by night feeding-induced changes in IPC firing characteristics and sxe2 levels in the fat body. These findings indicate circuit-level regulation of metabolism by clock cells in Drosophila and support a role for the pars intercerebralis in integrating circadian control of behavior and physiology.
authors.affiliation: Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Annika F
authors.initials: AF
authors.lastname: Barber
authors.affiliation: Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Renske
authors.initials: R
authors.lastname: Erion
authors.affiliation: Department of Physiology and Biophysics, University of California at Irvine, Irvine, California 92697, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Holmes
authors.affiliation: Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Amita
authors.initials: A
authors.lastname: Sehgal
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003463:Cues; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004435:Eating; D055590:Electromagnetic Phenomena; D005216:Fat Body / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D007328:Insulin
keywords: Drosophila; circadian; clock; electrophysiology; insulin; metabolism