Neural clocks and Neuropeptide F/Y regulate circadian gene expression in a peripheral metabolic tissue

Abstract
Article and author information
Metrics

Abstract

Metabolic homeostasis requires coordination between circadian clocks in different tissues. Also, systemic signals appear to be required for some transcriptional rhythms in the mammalian liver and the Drosophila fat body. Here we show that free-running oscillations of the fat body clock require clock function in the PDF-positive cells of the fly brain. Interestingly, rhythmic expression of the cytochrome P450 transcripts, sex-specific enzyme 1 (sxe1) and Cyp6a21, which cycle in the fat body independently of the local clock, depends upon clocks in neurons expressing neuropeptide F (NPF). NPF signaling itself is required to drive cycling of sxe1 and Cyp6a21 in the fat body, and its mammalian ortholog, Npy, functions similarly to regulate cycling of cytochrome P450 genes in the mouse liver. These data highlight the importance of neuronal clocks for peripheral rhythms, particularly in a specific detoxification pathway, and identify a novel and conserved role for NPF/Npy in circadian rhythms.

Article and author information

Author details

Renske Erion

Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States

Competing interests
The authors declare that no competing interests exist.
Anna N King

Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States

Competing interests
The authors declare that no competing interests exist.
Gang Wu

Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States

Competing interests
The authors declare that no competing interests exist.
John B Hogenesch

Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, United States

Competing interests
The authors declare that no competing interests exist.
Amita Sehgal

Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States

For correspondence
amita@mail.med.upenn.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of Pennsylvania.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.