Distinct transcriptomic effects of intermittent and chronic caloric restriction in mammary fat pad of a breast cancer mouse model

Bilge Guvenc Tuna; Nazim Arda Keles; Munevver Burcu Cicekdal; Soner Dogan; Sulev Koks

doi:10.1371/journal.pone.0331898

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Distinct transcriptomic effects of intermittent and chronic caloric restriction in mammary fat pad of a breast cancer mouse model

Journal article

Open access

Peer reviewed

Distinct transcriptomic effects of intermittent and chronic caloric restriction in mammary fat pad of a breast cancer mouse model

Bilge Guvenc Tuna, Nazim Arda Keles, Munevver Burcu Cicekdal, Soner Dogan and Sulev Koks

PloS one, Vol.20(9), e0331898

2025

DOI: https://doi.org/10.1371/journal.pone.0331898

PMID: 40986521

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Abstract

Adipose Tissue - metabolism

Animals

Breast Neoplasms - genetics

Breast Neoplasms - metabolism

Breast Neoplasms - pathology

Caloric Restriction - methods

Disease Models, Animal

Female

Gene Expression Profiling

Mammary Glands, Animal - metabolism

Mammary Neoplasms, Experimental - genetics

Mammary Neoplasms, Experimental - metabolism

Mice

Mice, Inbred C57BL

Mice, Transgenic

Transcriptome

Age-related dysfunction in neuroendocrine signaling, which influences adipose tissue homeostasis, has been implicated in numerous diseases, including breast cancer. Caloric restriction has been shown to improve metabolic health and prolong lifespan, yet the molecular mechanisms underlying its long-term effects are not fully understood. In this study, we investigated the impact of long-term chronic (CCR) and intermittent caloric restriction (ICR) on the whole transcriptome of mammary fat pad tissue (MFP) in a breast cancer mouse model. Transgenic female Mouse Mammary Tumor Virus-Transforming Growth Factor-Alpha (MMTV-TGF-ɑ) C57BL/6 mice were randomized into ad libitum (AL), CCR, and ICR groups. Total RNA was isolated from the samples collected at weeks 10 (baseline), 49/50 (adult), and 81/82 (old), were then subjected to RNA sequencing. Differential gene expression analysis identified significant age-related transcriptomic shifts. Specifically, Malat1 expression levels, a long non-coding RNA associated with cancer progression, were elevated with aging, suggesting increased tumorigenic susceptibility in this model. Pathways linked to neuroendocrine signaling were downregulated with age, reflecting a potential decline in neuro-adipose cross-talk. Remarkably, ICR appeared to mitigate this age-related decline in neuroendocrine signaling by upregulating genes involved in neurotransmitter support and downregulating extracellular matrix organization and positive regulation of angiogenesis. In contrast, CCR did not effectively alter the whole transcriptome profile, particularly in long-term. Our findings reveal that ICR mitigates age-related transcriptional shifts in MFP tissue, providing a novel insight into dietary strategies for maintaining adipose tissue function with potential implications for cancer susceptibility.

Details

Title: Distinct transcriptomic effects of intermittent and chronic caloric restriction in mammary fat pad of a breast cancer mouse model
Authors/Creators: Bilge Guvenc Tuna - Yeditepe University
Nazim Arda Keles - Yeditepe University
Munevver Burcu Cicekdal - Ghent University
Soner Dogan - Yeditepe University
Sulev Koks - Murdoch University, Personalised Medicine Centre
Publication Details: PloS one, Vol.20(9), e0331898
Publisher: Public Library of Science
Identifiers: 991005815049207891
Murdoch Affiliation: Personalised Medicine Centre
Language: English
Resource Type: Journal article

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