Evidence mapPaperPMID 33495474Full record

ArticleNature communications2021

Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models.

Manasi Das, Lesley G Ellies, Deepak Kumar, Consuelo Sauceda, Alexis Oberg, Emilie Gross, Tyler Mandt, Isabel G Newton, Mehak Kaur, Dorothy D Sears and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
8.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.

  1. Pooled it
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  7. Metastasis in biological time.Frontiers in cell and developmental biology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Manasi DasVA San Diego Healthcare System, San Diego, CA, USA.
Lesley G ElliesDepartment of Pathology, University of California San Diego, La Jolla, CA, USA.
Deepak KumarVA San Diego Healthcare System, San Diego, CA, USA.
Consuelo SaucedaVA San Diego Healthcare System, San Diego, CA, USA.
Alexis ObergVA San Diego Healthcare System, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-6920-6467
Emilie GrossVA San Diego Healthcare System, San Diego, CA, USA.
Tyler MandtDepartment of Radiology, University of California, San Diego, La Jolla, CA, USA.
Isabel G NewtonDepartment of Radiology, University of California, San Diego, La Jolla, CA, USA.
Mehak KaurDepartment of Medicine, Division of Endocrinology and Metabolism, University of California San Diego, La Jolla, CA, USA.
Dorothy D SearsDepartment of Medicine, Division of Endocrinology and Metabolism, University of California San Diego, La Jolla, CA, USA.
Nicholas J G WebsterVA San Diego Healthcare System, San Diego, CA, USA. nwebster@health.ucsd.edu.ORCID http://orcid.org/0000-0002-3827-5750
University of California San Diego · USUC San Diego Health System · USVA San Diego Healthcare System · US

Funding

VIRAL MALIGNANCYP30CA023100 · UNIVERSITY OF CALIFORNIA SAN DIEGO · 1985 to 2005
$23.4M
Pilot & Feasibility ProgramP30DK063491 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2003 to 2025
$5.4M
Time-restricted feeding and breast cancerR01CA196853 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2025 to 2025
$317k
Training Clinical Scientists in Radiological ImagingT32EB005970 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2025 to 2025
$92k
BLR&D Research Career Scientist Award ApplicationIK6BX005224 · VA SAN DIEGO HEALTHCARE SYSTEM · 2025 to 2025
REGULATION OF LEYDIG CELL FUNCTIONSP50HD012303 · UNIVERSITY OF CALIFORNIA SAN DIEGO · 1985 to 1997
BLRD VA I01 BX002709BLRD VA I01 BX004848BLRD VA IK6 BX005224NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA196853NCI NIH HHS U54 CA155435NIBIB NIH HHS T32 EB005970NICHD NIH HHS P50 HD012303NIDDK NIH HHS P30 DK063491
6 · The paper itself

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.

Indexed as

Disease Models, AnimalFastingAnimalsBreast NeoplasmsCaloric RestrictionCell Line, TumorDiet, High-FatFemaleHumansHyperinsulinismInsulin ResistanceMiceMice, Inbred C57BLMice, ObeseObesityOvariectomy

Identifiers

PMID33495474
PMCPMC7835248
OpenAlexW3121759644

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.