Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models
Das M, Ellies LG, Kumar D, Sauceda C, Oberg A, Gross E, Mandt T, Newton IG, Kaur M, Sears DD, Webster NJG
Nature communications · 74 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- U.S. Department of Veterans Affairs
- Government
- National Institutes of Health
- University or hospital
- University of California, San Diego
- Government
- National Cancer Institute
- Government
- National Institute of Diabetes and Digestive and Kidney Diseases
- Government
- National Institute of Biomedical Imaging and Bioengineering
- Government
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Government
- NCI NIH HHS
- Government
- NICHD NIH HHS
- Government
- BLRD VA
- Government
- NIDDK NIH HHS
- Government
- NIBIB NIH HHS
- Grants
- National Cancer Institute (R01 CA196853); National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK063491); U.S. Department of Veterans Affairs (IK6 BX005224); U.S. Department of Veterans Affairs (I01 BX004848); National Institute of Biomedical Imaging and Bioengineering (T32EB005970); U.S. Department of Veterans Affairs (I01 BX002709); Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD012303); National Cancer Institute (U54-CA155435); National Cancer Institute (P30 CA023100); National Institutes of Health (CA196853); National Institutes of Health (CA023100); National Institutes of Health (CA155435)
Based on 12 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2021-01-25 · Nat Commun · vol. 12 · issue 1 · p. 565
- Publisher
- Nature Portfolio
- Cited
- 92 citations · more than 99% of similar papers · 8.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 90 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Dietary Effects on Health · Diet and metabolism studies · Circadian rhythm and melatonin
- Keywords
- Hyperinsulinemia, Endocrinology, Internal medicine, Breast cancer, Cancer, Medicine, Insulin, Calorie restriction, Mammary tumor, Insulin resistance, Carcinogenesis, Cancer research, Biology
- MeSH
- cell line, tumor, animals, mice, inbred c57bl, humans, mice, mice, obese, breast neoplasms, hyperinsulinism, insulin resistance, obesity, disease models, animal, caloric restriction, ovariectomy, fasting, postmenopause, female, diet, high-fat
11 authors
From US
- Manasi DasUniversity of California San Diego; VA San Diego Healthcare System
- Lesley G. ElliesUniversity of California San Diego
- Deepak KumarUniversity of California San Diego; VA San Diego Healthcare System
- Consuelo SaucedaUniversity of California San Diego; VA San Diego Healthcare System
- Alexis ObergVA San Diego Healthcare System
- Emilie T. E. GrossUniversity of California San Diego; VA San Diego Healthcare System
Abstract
Accumulating evidence indicates that obesity with its associated metabolic dysregulation, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Caloric restriction can ameliorate the harmful metabolic effects of obesity and inhibit cancer progression but is difficult to implement and maintain outside of the clinic. In this study, we aim to test a time-restricted feeding (TRF) approach on mouse models of obesity-driven postmenopausal breast cancer. We show that TRF abrogates the obesity-enhanced mammary tumor growth in two orthotopic models in the absence of calorie restriction or weight loss. TRF also reduces breast cancer metastasis to the lung. Furthermore, TRF delays tumor initiation in a transgenic model of mammary tumorigenesis prior to the onset of obesity. Notably, TRF increases whole-body insulin sensitivity, reduces hyperinsulinemia, restores diurnal gene expression rhythms in the tumor, and attenuates tumor growth and insulin signaling. Importantly, inhibition of insulin secretion with diazoxide mimics TRF whereas artificial elevation of insulin through insulin pumps implantation reverses the effect of TRF, suggesting that TRF acts through modulating hyperinsulinemia. Our data suggest that TRF is likely to be effective in breast cancer prevention and therapy.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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