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Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges
Open accessAbstract
Because current therapeutics for obesity are limited and only offer modest improvements, novel interventions are needed. Preventing obesity with time-restricted feeding (TRF; 8-9 hr food access in the active phase) is promising, yet its therapeutic applicability against preexisting obesity, diverse dietary conditions, and less stringent eating patterns is unknown. Here we tested TRF in mice under diverse nutritional challenges. We show that TRF attenuated metabolic diseases arising from a variety of obesogenic diets, and that benefits were proportional to the fasting duration. Furthermore, protective effects were maintained even when TRF was temporarily interrupted by ad libitum access to food during weekends, a regimen particularly relevant to human lifestyle. Finally, TRF stabilized and reversed the progression of metabolic diseases in mice with preexisting obesity and type II diabetes. We establish clinically relevant parameters of TRF for preventing and treating obesity and metabolic disorders, including type II diabetes, hepatic steatosis, and hypercholesterolemia.
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“Later mouse studies have demonstrated benefits of TRF when using multiple variations of dietary and temporal control and also suggest that TRF can even stabilize or reverse the progression of metabolic diseases (85).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [85]
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The role of intermittent fasting and ketogenic diet in metabolic syndrome and type 2 diabetes
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Time-restricted feeding ameliorates maternal high-fat diet-induced fetal lung injury
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“Similarly, TRF can help improve metabolic health by altering clock function [14].”
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“A TR ND group was not included in the current study because previous studies [23,25,27] found no significant differences in cardiometabolic parameters between ad libitum ND and TR ND groups.”
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“Other studies have also reported the beneficial effects of time-restricted feeding, which prevents not only excessive weight gain [12–14], but also fat accumulation and associated inflammation, glucose intolerance and insulin resistance, as well as improves nutrient homeostasis [14].”
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“In addition, pigs on the M2 regimen showed a decreased TG concentration in the serum and liver, which is consistent with the results of previous studies on pigs or rodents [2,18,19].”
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“Their roles are diverse, which include providing nutrients to the host by degrading food residues in the gut, developing immunity, and affecting mind and behavior (Osawa et al., 1995; Forsythe et al., 2010; Ray et al., 2012; Chaix et al., 2014; Ohno, 2020).”
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“Timing of diet, and various paradigms of TRF, 15,16 are known to influence circadian rhythmicity, but have not been examined in leukemia models.”
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Temporal Orchestration of Immunity: How Circadian Clocks Coordinate Immune Responses
Jiang, Y., Liu, C., & Zhong, Y. (2025) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl39948 · Cited by 5
“Disruption in light hygiene (e.g., shift work, screen light exposure, irregular sleep) has been shown to reduce microbiota diversity, decrease SCFA levels, and compromise intestinal epithelial integrity [126,127].”
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“The interventions such as time-restricted feeding are proposed to have beneficial effects in the prevention and treatment of metabolic diseases (Chaix et al. 2014).”
Matz‐Soja, M., Körner, C., Ott, F., Fischer, J., Marbach-Breitrück, E., Bergmann, C., Hofmann, U., Shevchenko, A., Wallach, I., Textoris‐Taube, K., et al. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-06046-4 · Cited by 5
“Previous studies have shown that TRF enhances hepatic metabolic rhythms and improves systemic insulin sensitivity in mice, even without caloric restriction [33, 75].”
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Kędzierska-Kapuza, K., Łopuszyńska, I., Niewiński, G., Franek, E., & Szczuko, M. (2024) · Nutrients · doi:10.3390/nu16183216 · Cited by 5
“Similarly, in rodents, time-restricted feeding helped prevent weight gain from high-fat, high-sucrose diets and improved overall body composition [63,64].”
Prates, K. V., Pavanello, A., Gôngora, A. B., Moreira, V. M., de Moraes, A. M. P., Palma‐Rigo, K., Vieira, E. C., & Mathias, P. C. D. F. (2022) · Nutrition · doi:10.1016/j.nut.2022.111776 · Cited by 5
Chen, W. W., Wang, L., Zhou, A. J., Fan, C., Zhang, Y. D., Wang, Z. P., Rong, S., & Wang, T. (2023) · Acta Alimentaria · doi:10.1556/066.2022.00230 · Cited by 5
“Recent preclinical studies in rodents suggest that TRF may exert vascular protective effects by attenuating pro-inflammatory processes (Hatori et al., 2012; Chaix et al., 2014; Sutton et al., 2018).”
BackgroundWeight management in primary care: the call for a practical and evidence-informed approach
Rathomi, H. S., Mavaddat, N., Katzenellenbogen, J. M., & Thompson, S. (2023) · Family Practice · doi:10.1093/fampra/cmad101 · Cited by 5
Environmental regulation of metabolism through the circadian clock
Escalante‐Covarrubias, Q., & Aguilar‐Arnal, L. (2018) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2018.03.003 · Cited by 5
Persinger, A., Butawan, M. B., Faietti, M., Pryke, A., Rose, K., van der Merwe, M., Bloomer, R. J., & Puppa, M. (2021) · Nutrients · doi:10.3390/nu13051717 · Cited by 5
“These previous studies point toward an improvement in metabolic flexibility when consuming a high-fat diet [3,4,7].”
BackgroundDevelopment and validation of the Chrononutrition Profile – Diary
Veronda, A. C., Allison, K. C., Crosby, R. D., & Irish, L. A. (2022) · Eating Behaviors · doi:10.1016/j.eatbeh.2022.101625 · Cited by 5
Sanetra, A. M., Palus‐Chramiec, K., Chrobok, Ł., & Lewandowski, M. H. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15759 · Cited by 5
“Bidirectional relationship between dysregulated circadian feeding pattern and obesity has been shown both in humans as well as in animal models (Chaix et al., 2014; Chrobok, Klich, Jeczmien-Lazur, et al., 2022; Hatori et al., 2012; Kohsaka et al., 2007).”
MethodTime-restricted eating as a novel strategy for treatment of obesity and it’s comorbid conditions
Berkovskaya, M. A., Gurova, O. Y., Khaykina, I. A., & Fadeev, V. V. (2022) · Problems of Endocrinology · doi:10.14341/probl13078 · Cited by 6
Kesztyüs, D., Schönsteiner, D., Gulich, M., & Kesztyüs, T. (2020) · doi:10.21203/rs.2.20835/v1 · Cited by 5
Golpour-Hamedani, S., Askari, G., Khorvash, F., Kesharwani, P., Bagherniya, M., & Sahebkar, A. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149348 · Cited by 5
Time-Restricted Feeding Attenuates Salt-Sensitive Hypertension and Renal Damage
Yunker, L., Usa, K., Williams, A. C., Reho, J. J., Grobe, J. L., Gumz, M. L., & Kriegel, A. J. (2025) · Hypertension · doi:10.1161/hypertensionaha.125.24857 · Cited by 4
Time-restricted feeding extends healthspan in both sexes and lifespan in male C57BL/6 J mice
Iiams, S. E., Skinner, N. J., Wight‐Carter, M., Acosta-Rodríguez, V. A., Green, C. B., & Takahashi, J. S. (2026) · Nature Aging · doi:10.1038/s43587-026-01129-8 · Cited by 6
“These findings, along with evidence that TRF 5 out of 7 days per week regimens still improves metabolic health in mice 37 and lifespan in flies 93 , suggest that moderate TRE adherence may still prolong healthspan and be compatible with modern human lifestyles.”
Selingardi, S. D. A., Ribeiro, S. M. L. T., de Freitas, S. N., Pimenta, F. A. P., Machado-Coelho, G. L. L., de Oliveira, F. L. P., Neto, R. M. D. N., & de Menezes-Júnior, L. A. A. (2024) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2024.04.023 · Cited by 4
Tan, Y., Li, M., Li, H., Guo, Y., Zhang, B., Wu, G., Li, J., Zhang, Q., Sun, Y., Gao, F., et al. (2024) · Advanced Science · doi:10.1002/advs.202407677 · Cited by 4
Li, Y., Fujihara, H., Fujisawa, K., & Kawai, K. (2024) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.24-220 · Cited by 5
“(11,12) This interaction plays a role in metabolic disorders and obesity, and in optimizing exercise performance.”
Hu, L., Tang, H., Xie, Z., Yi, H., Feng, L., Zhou, P., Zhang, Y., Liu, J., Ao, X., Zhou, J., et al. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1510354 · Cited by 4
Chakraborty, P., Dromard, Y., André, E. M., Dedin, M., Arango-Lievano, M., Raner, A., Besnard, A., Santos‐Silva, T., Helbling, J., Ferreira, G., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105783 · Cited by 5
“32,33 This regimen was chosen over shorter TRF durations (2 weeks, 34 ) that has been reported in adult mice treated with HFD for 18 weeks, but not adolescent mice as in this study.”
Ramadan Fasting: Influences on Sleep, Circadian Rhythms, Mealtime, and Metabolic Health
BaHammam, A. S., & Qasrawi, S. O. (2025) · Springer eBooks · doi:10.1007/978-981-96-6783-3_6 · Cited by 4
JARID1a Ablation in the Liver Alters Systemic Metabolism and Adaptation to Feeding
DiTacchio, K. A., Kalinowska, D., Saran, A., Byrne, A., Vollmers, C., & DiTacchio, L. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107668 · Cited by 4
“Conversely, improvement of the circadian function via feedingschedule manipulation is able to prevent and reverse the deleterious effects of high-fat diet (HFD) in mice (Chaix et al., 2014; Hatori et al., 2012), underscoring the importance of the circadian system in the maintenance of metabolic homeostasis.”
Backgroundde Oliveira, D. A., Araújo, N. C. D. M., Freire, A. R., Albuquerque, G. S., Muniz, G. D. S., & do Nascimento, E. (2021) · Biological Rhythm Research · doi:10.1080/09291016.2021.1973203 · Cited by 6
“Another study did not observe a difference in weight between restricted animals compared to non-restricted animals (Chaix et al. 2014).”
ResultAkowuah, P. K., Lema, C., Rumbaut, R. E., & Burns, A. R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24020931 · Cited by 4
“This is also the case in other published mouse models of diet-induced obesity [34,69,70].”
MethodResultTransient anticonvulsant effects of time-restricted feeding in the 6-Hz mouse model
Armstrong, O. J., Neal, E. S., Vidovic, D., Xu, W., & Borges, K. (2024) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2023.109618 · Cited by 4
“Consistent with the latter explanations, continuous and 2:5 TRF have been associated with increased glucose tolerance and reduced insulin resistance [78].”
BackgroundBravo-García, A. P., Radford, B. E., Hall, R. C., Broome, S. C., Tee, N., Arthur, B., Janssens, K., Johnston, R. D., Halson, S. L., Devlin, B. L., et al. (2025) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2025.112081 · Cited by 10
“TRE aligns the timing of the meals with biological circadian rhythms, optimising metabolic adaptations that enhance glucose management [8,9].”
Reynolds, J. S., Peng, W., Chu, T., & Mitchell, J. R. (2018) · Nutrition and Healthy Aging · doi:10.3233/nha-180044 · Cited by 4
Costa, A. C. O., Araújo, N. C. D. M., Muniz, G. D. S., de Souza, S. L., & do Nascimento, E. (2021) · Biological Rhythm Research · doi:10.1080/09291016.2021.1882143 · Cited by 4
“Previously, it has been shown that dietary restriction can be positive in weight loss in unbalanced dietary conditions and that the effects seem to be proportionate to the duration of fasting (Chaix et al. 2014).”
BackgroundAttal, K., Wickman, J. A., Kojima, S., Blythe, S. G., & Toporikova, N. (2021) · Obesity Medicine · doi:10.1016/j.obmed.2021.100347 · Cited by 4
The impact of circadian timing on energy balance: an extension of the energy balance model
Veronda, A. C., Kline, C. E., & Irish, L. A. (2021) · Health Psychology Review · doi:10.1080/17437199.2021.1968310 · Cited by 4
“These findings have been replicated in mice by other researchers (Chaix et al., 2014; Hatori et al., 2012).”
MethodResultDiet and Circadian Rhythms: Implications for Aging and Longevity
Jagota, A., Khan, Z. A., & Khan, M. S. (2021) · Healthy ageing and longevity · doi:10.1007/978-3-030-83017-5_19 · Cited by 4
Nocturnal and Diurnal Behavior Assessed by the “Work-for-Food” Protocol in Small Rodents
van Rosmalen, L., Riede, S. J., Pilorz, V., Adage, T., Scheurink, A. J. W., van der Vinne, V., & Hut, R. A. (2022) · Neuromethods · doi:10.1007/978-1-0716-2577-4_9 · Cited by 4
Antonio, G. C. F., da Silva, A. S. R., de Freitas, E. C., & Pauli, J. R. (2023) · Obesities · doi:10.3390/obesities3030018 · Cited by 4
Metadata
- Authors
- Chaix, A., Zarrinpar, A., Miu, P., & Panda, S.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Panda, Satchidananda
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 20
- Issue
- 6
- Pages
- 991-1005
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4255155
- OpenAlex
- W2171666144
- Cited by
- 956
- References
- 43
- Citations by year
- 2026: 77 · 2025: 83 · 2024: 90 · 2023: 88 · 2022: 118 · 2021: 123 · 2020: 112 · 2019: 70 · 2018: 59 · 2017: 56 · 2016: 44 · 2015: 35
- FWCI
- 30.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- American Association for the Study of Liver Diseases
- Leona M. and Harry B. Helmsley Charitable Trust
- Philippe Foundation
- National Institutes of Health
- National Eye Institute (R01EY016807, P30EY019005, EY016807)
- National Cancer Institute (P30CA014195)
- National Institute of General Medical Sciences (P50GM085764)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK080506, T32-DK07202, R01DK091618, T32DK007202, DK091618-04)
- National Institute of Neurological Disorders and Stroke (NS066457, R21NS066457)
- National Center for Research Resources (S10RR027450)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- time-restricted feeding, obesity prevention, type 2 diabetes, metabolic disorders, fasting duration, obesogenic diet, hepatic steatosis, hypercholesterolemia, intermittent fasting, ad libitum feeding
- MeSH terms
- Animals, Energy Intake, Diabetes Mellitus, Type 2, Dietary Fats, Feeding Behavior, Metabolic Diseases, Mice, Inbred C57BL, Obesity, Time Factors, Weight Gain, Mice
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