Plasma Metabolomic Changes in Mice With Time-restricted Feeding-attenuated Spontaneous Metastasis of Lewis Lung Carcinoma

Yan, Lin; Rust, Bret; Picklo, Matthew J.

doi:10.21873/anticanres.14137

Cited by 10 publications

(5 citation statements)

References 42 publications

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“…Although data are limited to a few animal studies, TRF intervention has been shown to have an antineoplastic effect in various cancers [ 15 – 17 , 20 ]. Animal or population evidences of TRF effect on lung cancer are however arising from only two experiments [ 19 , 43 ]. Both studies have found that 12-h TRF abrogated the obesity-enhanced spontaneous metastasis of Lewis lung cancer, as well as restored the health phenotypic impairment or shifted the plasma metabolic profiles changes driven by high-fat diet [ 19 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…Animal or population evidences of TRF effect on lung cancer are however arising from only two experiments [ 19 , 43 ]. Both studies have found that 12-h TRF abrogated the obesity-enhanced spontaneous metastasis of Lewis lung cancer, as well as restored the health phenotypic impairment or shifted the plasma metabolic profiles changes driven by high-fat diet [ 19 , 43 ]. Although the above studies have both demonstrated the potential inhibitory effects of 12-h TRF on lung cancer metastasis within the context of high-fat diet-induced obesity, the impact of TRF on lung cancer growth and progression in nonobese animals remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

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Six-hour time-restricted feeding inhibits lung cancer progression and reshapes circadian metabolism

Shi,

Fang,

Chen

et al. 2023

BMC Med

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Background Accumulating evidence has suggested an oncogenic effect of diurnal disruption on cancer progression. To test whether targeting circadian rhythm by dietary strategy suppressed lung cancer progression, we adopted 6-h time-restricted feeding (TRF) paradigm to elucidate whether and how TRF impacts lung cancer progression. Methods This study used multiple lung cancer cell lines, two xenograft mouse models, and a chemical-treated mouse lung cancer model. Stable TIM-knockdown and TIM-overexpressing A549 cells were constructed. Cancer behaviors in vitro were determined by colony formation, EdU proliferation, wound healing, transwell migration, flow cytometer, and CCK8 assays. Immunofluorescence, pathology examinations, and targeted metabolomics were also used in tumor cells and tissues. mCherry-GFP-LC3 plasmid was used to detect autophagic flux. Results We found for the first time that compared to normal ad libitum feeding, 6-h TRF inhibited lung cancer progression and reprogrammed the rhythms of metabolites or genes involved in glycolysis and the circadian rhythm in tumors. After TRF intervention, only timeless (TIM) gene among five lung cancer-associated clock genes was found to consistently align rhythm of tumor cells to that of tumor tissues. Further, we demonstrated that the anti-tumor effect upon TRF was partially mediated by the rhythmic downregulation of the TIM and the subsequent activation of autophagy. Combining TRF with TIM inhibition further enhanced the anti-tumor effect, comparable to treatment efficacy of chemotherapy in xenograft model. Conclusions Six-hour TRF inhibits lung cancer progression and reshapes circadian metabolism, which is partially mediated by the rhythmic downregulation of the TIM and the subsequent upregulation of autophagy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Six-hour time-restricted feeding inhibits lung cancer progression and reshapes circadian metabolism

Shi,

Fang,

Chen

et al. 2023

BMC Med

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“…3-Hydroxybutyric acid is a main ketone body generated from excessive acetyl-CoA production resulting from hepatic β-oxidation; it is an indicator of excessive lipid oxidation and potential mitochondrial dysfunction (45,46). Previous studies have shown that TRF elevates 3-hydroxybutyric acid in plasma (47,48). Decrements of this ketone body in mammary tumors by TRF suggest an increase in utilization of this energy source by the tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions

et al. 2020

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Background/Aim: Time restricted feeding (TRF) mitigates the high-fat diet-enhanced mammary tumorigenesis in a MMTV-PyMT breast cancer model. Materials and Methods: We performed untargeted metabolomic and targeted transcriptomic analyses on mammary tumors from MMTV-PyMT mice fed a standard AIN93G diet, a high-fat diet (HFD), or HFD with TRF (12 h, dark phase) and mammary glands from wild-type mice fed the AIN93G diet. Results: The metabolic profile of mammary tumors differed from that of mammary glands; there was no impact of TRF upon tumor metabolome. TRF did reduce elevated expression of Hmgcr, Srebp1, Fads2, and Ppard in mammary tumors, indicating a down-regulation of lipid metabolism. Conclusion: The null effect of TRF on the metabolomic profile does not rule out changes in more refined intracellular signaling pathways. It suggests that the protection of TRF against mammary tumorigenesis may rely upon its action on the host rather than a direct effect on tumor metabolism.

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“…They also observed that TRF decreased the phosphorylation of AKT (also known as PKB, protein kinase B) in tumor tissues, supporting the idea that TRF may be related to autophagy. Yan et al [49–51] also demonstrated that TRF could attenuate the spontaneous metastasis of Lewis lung cancer and reduce the expression of oncogenic genes through a series of animal experiments.…”

Section: Potential Antitumor Effects Of Trementioning

confidence: 99%

Potential preventive effects of time-restricted eating on cancer

Fang,

Yan,

Liao

2023

J Nutr Oncol

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Intermittent fasting is a novel dietary intervention that has been demonstrated to improve the efficacy of cancer therapy and reduce complications. Time-restricted eating is a specific form of intermittent fasting. It usually restricts only the daily eating window and not the amount of calories consumed. In addition to providing a means for weight management and improving metabolism like other intermittent fasting methods, time-restricted eating also synchronizes circadian rhythms and affects autophagy levels, which has potential antiaging effects. Some studies have shown that time-restricted eating can prevent tumorigenesis and slow tumor progression. Moreover, because of its simplicity and mild adverse effects, time-restricted eating is safe and has a high rate of compliance. It may be used an adjuvant therapy and may be part of a healthy lifestyle suitable for long term by cancer patients or those at high risk of developing specific cancers. This article expounds on the potential impact of time-restricted eating on the prevention and treatment of cancer, as well as the potential mechanism(s) of action. There are 3 main aspects considered to be impacted by time-restricted eating: improving obesity and metabolic disorders, synchronizing the circadian rhythm, and upregulating autophagy. We herein present the current research progress related to the effects of time-restricted eating on malignant tumors. The purpose of this review is to provide a theoretical basis and direction for future research to explore the potential of time-restricted eating as a nutritional intervention to prevent the occurrence of cancer and as a treatment or adjuvant therapy for cancer. We believe that this approach may be conducive to improving the nutritional status of cancer patients and improving their prognosis and quality of life.

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Plasma Metabolomic Changes in Mice With Time-restricted Feeding-attenuated Spontaneous Metastasis of Lewis Lung Carcinoma

Cited by 10 publications

References 42 publications

Six-hour time-restricted feeding inhibits lung cancer progression and reshapes circadian metabolism

Six-hour time-restricted feeding inhibits lung cancer progression and reshapes circadian metabolism

Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions

Potential preventive effects of time-restricted eating on cancer

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