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

ABSTRACT: 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.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.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.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.ISRCTN77916487 31/07/2012.

SUBMITTER: Harvie MN

PROVIDER: S-EPMC4884347 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Harvie Michelle N MN Sims Andrew H AH Pegington Mary M Spence Katherine K Mitchell Adam A Vaughan Andrew A AA Allwood J William JW Xu Yun Y Rattray Nicolas J W NJ Goodacre Royston R Evans D Gareth R DG Mitchell Ellen E McMullen Debbie D Clarke Robert B RB Howell Anthony A

Breast cancer research : BCR 20160528 1

<h4>Background</h4>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.<h4>Methods</h4>We assessed the effect of IER (two days of 65 % energy restriction per week) for one menstrual cycle on breast tissue ...[more]

PMID: 27233359

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Project description:Background Intermittent energy restriction (IER) is an effective weight loss strategy. However, the accompanying changes in spontaneous neural activity are unclear, and the relationship among anthropometric measurements, biochemical indicators, and adipokines remains ambiguous. Methods Thirty-five obese adults were recruited and received a 2-month IER intervention. Data were collected from anthropometric measurements, blood samples, and resting-state functional magnetic resonance imaging at four time points. The regional homogeneity (ReHo) method was used to explore the effects of the IER intervention. The relationships between the ReHo values of altered brain regions and changes in anthropometric measurements, biochemical indicators, and adipokines (leptin and adiponectin) were analyzed. Results Results showed that IER significantly improved anthropometric measurements, biochemical indicators, and adipokine levels in the successful weight loss group. The IER intervention for weight loss was associated with a significant increase in ReHo in the bilateral lingual gyrus, left calcarine, and left postcentral gyrus and a significant decrease in the right middle temporal gyrus and right cerebellum (VIII). Follow-up analyses showed that the increase in ReHo values in the right LG had a significant positive correlation with a reduction in Three-factor Eating Questionnaire (TFEQ)-disinhibition and a significant negative correlation with an increase in TFEQ-cognitive control. Furthermore, the increase in ReHo values in the left calcarine had a significant positive correlation with the reduction in TFEQ-disinhibition. However, no significant difference in ReHo was observed in the failed weight loss group. Conclusion Our study provides objective evidence that the IER intervention reshaped the ReHo of some brain regions in obese individuals, accompanied with improved anthropometric measurements, biochemical indicators, and adipokines. These results illustrated that the IER intervention for weight loss may act by decreasing the motivational drive to eat, reducing reward responses to food cues, and repairing damaged food-related self-control processes. These findings enhance our understanding of the neurobiological basis of IER for weight loss in obesity.

Project description:Lymphocyte and breast tissue samples from overweight woman at increased risk of breast cancer before and after 1 month of intermittant energy restriction Introduction Observational studies indicate that weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight as well as, or more than continuous energy restriction (CER), but its effect on the breast and systemic metabolism as indicators of breast cancer risk are not known. Methods We assessed the effect of IER ( 2 days of 65% energy restriction) for one menstrual cycle on the breast (breast gene expression and fat cell size) and systemic metabolism (insulin resistance, lipids, serum and urine metabolites) in 23 overweight premenopausal women at high risk of breast cancer. Unsupervised hierarchical analysis selected 100 genes with the highest variance between pre and post IER biopsies in 20 subjects, whilst mass spectrometry was used to assess corresponding changes in serum (LCMS) and urine metabolites (GCMS) in 23 subjects in the restricted and unrestricted days of the IER. Results Women lost on average 4.8% (± 2.0) of body weight and 8.0% (± 5.0) of body fat. Insulin resistance (HOMA) was reduced by 29.8% (±17.8) on the restricted days and by 11%(±34) on the unrestricted days of the IER. Over 250 serum and urine metabolites significantly increased or decreased during the two restricted days and most returned to normal after the subsequent five day period . In the breast tissue, approximately half (In 11) of the subjects displayed down regulation of several metabolic pathways including lipid synthesis, growth factors and hormones, whilst epithelial genes including milk proteins, secretoglobulins and mucins were up-regulated and several metabolic pathways down-regulated including lipid synthesis, growth factors and hormones. In the other nine subjects there was no appreciable effect of IER on the breast. CorrespondingThe gene changes were not seen in peripheral blood lymphocytes, and there was no reduction in breast fat cell size. The two groups defined by change in gene expression or lack of it did not differ in the degree of weight or fat loss, other systemic metabolic markers, or histological assessment of the biopsies. Conclusion We conclude that breasts vary in response to short-term IER, the mechanism of which requires further investigation. Trial registration ISRCTN77916487

Project description:PURPOSE:Intermittent energy restriction (IER) is a popular weight loss (WL) strategy; however, its efficacy in clinical practice remains unknown. The present study compared the effects of IER compared to continuous energy restriction (CER) on WL and cardiometabolic risk factors in primary care. METHODS:A (self-selected) cohort study was conducted at the Rotherham Institute for Obesity (RIO), a primary care-based weight management service. 197(24% male) obese patients volunteered to participate and selected their diet group. IER participants (n?=?99) consumed?~?2600 kJ for two days/week. CER participants (n?=?98) restricted their diet by?~?2100 kJ/day below estimated requirements. Both interventions were delivered alongside RIO standard care. Changes in anthropometry and cardiometabolic disease risk markers (fasting biochemistry and blood pressure) were assessed after a 6-month intervention period and then participants were followed up again 6 months later (month 12). RESULTS:27 IER patients (27%) and 39 CER patients (40%) completed the 6-month weight loss phase. Among completers, mean (SEM) WL was greater in the IER group at 6 months (5.4?±?1.1% versus 2.8?±?0.6%; p?=?0.01), as were reductions in fat mass (p?<?0.001) and improvements in systolic blood pressure (p?<?0.001). Fasting insulin (p?=?0.873) and diastolic blood pressure (p?=?0.701) were reduced similarly in both groups. However, in the IER group, changes in anthropometry and blood pressure in the IER group had reverted to baseline by 12-month follow-up, whilst the CER group maintained weight loss but showed an increase in blood pressure. CONCLUSIONS:Among completers, IER resulted in superior short-term changes in anthropometry and some cardiometabolic risk factors. However, rates of attrition and weight regain were higher compared with standard care, providing important insights in the implementations of IER within a "real-life" NHS setting. TRIAL REGISTRATION NUMBER:ISRCTN31465600.

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

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

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