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Breast Cancer Research
Published in: Breast Cancer Research 1/2016

Open Access 01-12-2016 | Research article

Intermittent energy restriction induces changes in breast gene expression and systemic metabolism

Authors: Michelle N. Harvie, Andrew H. Sims, Mary Pegington, Katherine Spence, Adam Mitchell, Andrew A. Vaughan, J. William Allwood, Yun Xu, Nicolas J. W. Rattray, Royston Goodacre, D. Gareth R. Evans, Ellen Mitchell, Debbie McMullen, Robert B. Clarke, Anthony Howell

Published in: Breast Cancer Research | Issue 1/2016

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Abstract

Background

Observational studies suggest weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight to the same extent as, or more than equivalent continuous energy restriction (CER) but the effects of IER on normal breast tissue and systemic metabolism as indicators of breast cancer risk are unknown.

Methods

We assessed the effect of IER (two days of 65 % energy restriction per week) for one menstrual cycle on breast tissue gene expression using Affymetrix GeneChips, adipocyte size by morphometry, and systemic metabolism (insulin resistance, lipids, serum and urine metabolites, lymphocyte gene expression) in 23 overweight premenopausal women at high risk of breast cancer. Unsupervised and supervised analyses of matched pre and post IER biopsies in 20 subjects were performed, whilst liquid and gas chromatography mass spectrometry assessed corresponding changes in serum and urine metabolites in all subjects after the two restricted and five unrestricted days of the IER.

Results

Women lost 4.8 % (±2.0 %) of body weight and 8.0 % (±5.0 %) of total body fat. Insulin resistance (homeostatic model assessment (HOMA)) reduced by 29.8 % (±17.8 %) on the restricted days and by 11 % (±34 %) on the unrestricted days of the IER. Five hundred and twenty-seven metabolites significantly increased or decreased during the two restricted days of IER. Ninety-one percent of these returned to baseline after 5 days of normal eating. Eleven subjects (55 %) displayed reductions in energy restriction-associated metabolic gene pathways including lipid synthesis, gluconeogenesis and glycogen synthesis. Some of these women also had increases in genes associated with breast epithelial cell differentiation (secretoglobulins, milk proteins and mucins) and decreased collagen synthesis (TNMD, PCOLCE2, TIMP4). There was no appreciable effect of IER on breast gene expression in the other nine subjects. These groups did not differ in the degree of changes in weight, total body fat, fat cell size or serum or urine metabolomic markers. Corresponding gene changes were not seen in peripheral blood lymphocytes.

Conclusion

The transcriptional response to IER is variable in breast tissue, which was not reflected in the systemic response, which occurred in all subjects. The mechanisms of breast responsiveness/non-responsiveness require further investigation.

Trial registration

ISRCTN77916487 31/07/2012.
Appendix
Available only for authorised users
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Metadata
Title
Intermittent energy restriction induces changes in breast gene expression and systemic metabolism
Authors
Michelle N. Harvie
Andrew H. Sims
Mary Pegington
Katherine Spence
Adam Mitchell
Andrew A. Vaughan
J. William Allwood
Yun Xu
Nicolas J. W. Rattray
Royston Goodacre
D. Gareth R. Evans
Ellen Mitchell
Debbie McMullen
Robert B. Clarke
Anthony Howell
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2016
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-016-0714-4

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