Time‐Restricted Feeding Attenuates Breast Cancer Growth in a Mouse Model of Postmenopausal Obesity
Authors: Das Manasi , Gross Emilie , Kumar Deepak , Sauceda Consuelo , Park Hyun‐Tae , Sears Dorothy , Ellies Lesley , Webster Nicholas 
Published: June 2021

BackgroundObesity continues to be a serious health issue worldwide and is mounting with time. Research indicates that obesity increases the risk for several cancers including breast cancer and the occurrence is further augmented by 40% in postmenopausal women. Therefore, effective and practical strategies that could have a far‐reaching impact are warranted to curb breast cancer risk in obese postmenopausal women. In this scenario, time‐restricted feeding (TRF), i.e.,consuming ad‐libitum energy during the normal active phase, has been shown to attenuate obesity‐driven metabolic dysregulations. However, implementation of TRF in a cancer setting has not been explored. Thus, the present study sought to understand the ability of TRF to enhance breast cancer remission in postmenopausal, obese female mice. Further, the work also explores the mechanistic link of TRF in reduced tumor growth.MethodsAs postmenopausal mice models, 4‐Vinylcyclohexene Diepoxide (VCD) treated or Ovariectomized mice were used. For the VCD model, mice were treated with VCD (160 mg/ml) for 15 days. The VCD and ovariectomized mice were fed a 60% high fat diet (HFD) to become obese and then grouped randomly into either an ad libitum group (24 hr access to food) or a TRF group (8 hr access to food during active phase) to evaluate the metabolic and tumor growth effect of TRF intervention. At 3 weeks following TRF, mice were injected with py230 breast cancer cells into the mammary fat pad for tumor development. Glucose tolerance test, pyruvate tolerance test, insulin tolerance test, lipid accumulation in liver by HE staining, body weight measurement, food intake, and measurement of the weight of different tissues assessed the metabolic effect of TRF. The change in tumor volume over time and tumor weight at time of harvest were measured to assess the effect of TRF on tumor growth. Also, insulin dependency of tumor growth was studied in mice fed with HFD with or without diazoxide in the ad libitum condition. Insulin dependent tumor growth was further confirmed in normal chow‐fed mice implanted with an insulin pump.ResultsThe studies in VCD treated or ovariectomized postmenopausal mice, revealed that confining access to western‐style HFD during active phase (night time) improves glucose tolerance, insulin resistance and hepatic steatosis without much change in quantity of food intake compared to the ad libitum group. Further, mice with TRF had reduced tumor growth in comparison to the ad libitum group in both models. More importantly, the results from the tumor growth study in mice fed with HFD with/without diazoxide or normal chow mice with/without insulin pump, suggest that the tumor growth is insulin‐dependent and TRF may act via attenuating insulin signaling.ConclusionThe results demonstrate that, TRF improves metabolic deregulation and reduces tumor growth in obese postmenopausal mice and imply that these effects are insulin‐dependent.Support or Funding InformationNIH/NCI RO1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.