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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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Time-Restricted Feeding Alters the Innate Immune Response to Bacterial Endotoxin
Cissé, Y. M., Borniger, J. C., Lemanski, E. A., Walker, W. H., & Nelson, R. J. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1701136 · Cited by 43
Zhao, L., Hutchison, A. T., Liu, B., Wittert, G., Thompson, C. H., Nguyen, L., Au, J., Vincent, A. D., Manoogian, E. N. C., Le, H. D., et al. (2022) · Obesity · doi:10.1002/oby.23499 · Cited by 39
“In mice with diet-induced obesity, TRE reduces body weight gain and body fat accumulation, improves glucose tolerance, and restores amplitude of core clock genes [6,7,11,12].”
BackgroundChrononutrition in type 2 diabetes mellitus and obesity: A narrative review
Verde, L., Lorenzo, T. D., Savastano, S., Colao, A., Barrea, L., & Muscogiuri, G. (2024) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3778 · Cited by 46
A nonrandomized controlled clinical pilot trial on 8 wk of intermittent fasting (24 h/wk)
Keßler, C. S., Stange, R., Schlenkermann, M., Jeitler, M., Michalsen, A., Selle, A., Raucci, F., & Steckhan, N. (2017) · Nutrition · doi:10.1016/j.nut.2017.08.004 · Cited by 42
Kentish, S. J., Hatzinikolas, G., Li, H., Frisby, C. L., Wittert, G., & Page, A. J. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0052-18.2018 · Cited by 41
Ren, J., Hu, D., Mao, Y., Yang, H., Liao, W., Xu, W., Ge, P., Zhang, H., Sang, X., Lü, X., et al. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14069 · Cited by 42
“Accumulated evidence has proved that TRF is a promising intervention against the worldwide trend of obesity.(1) TRF is also associated with reductions in serum total cholesterol, triglycerides (TG), glucose, insulin, interleukin 6 (IL‐6), tumour necrosis factor‐α (TNF‐α), as well as with improvements in insulin sensit…”
BackgroundComparison of time-restricted feeding and Islamic fasting: a scoping review
Ismail, S., Manaf, R. A., & Mahmud, A. (2019) · Eastern Mediterranean Health Journal · doi:10.26719/emhj.19.011 · Cited by 42
Kang, J., Ratamess, N. A., Faigenbaum, A. D., Bush, J. A., Beller, N. A., Vargas, A., Fardman, B., & Andriopoulos, T. (2021) · Journal of the American Nutrition Association · doi:10.1080/07315724.2021.1958719 · Cited by 44
Huang, S., Jiao, X., Lu, D., Pei, X., Qi, D., & Li, Z. (2021) · The Ocular Surface · doi:10.1016/j.jtos.2021.02.001 · Cited by 41
EGR1 regulates hepatic clock gene amplitude by activating Per1 transcription
Tao, W., Wu, J., Zhang, Q., Lai, S., Jiang, S., Chen, J., Xu, Y., Xue, B., Du, J., & Li, C. (2015) · Scientific Reports · doi:10.1038/srep15212 · Cited by 41
“Time-restricted feeding was reported to prevent metabolic diseases in mice that were fed a high-fat diet and represents a preventative and therapeutic intervention against diverse nutritional challenges 56,57 .”
Circadian- and Light-driven Metabolic Rhythms in Drosophila melanogaster
Rhoades, S. D., Nayak, K., Zhang, S., Sehgal, A., & Weljie, A. M. (2018) · Journal of Biological Rhythms · doi:10.1177/0748730417753003 · Cited by 39
“…28-h cyclers in our study to oscillate in other species, including zebrafish, mice, and humans (Li et al., 2015; Zwigahft et al., 2015; Giskeødegård et al., 2015; Davies et al., 2014; Chaix et al., 2014; Hatori et al., 2012; Eckel-Mahan et al., 2012; Dallmann et al., 2012; Ang et al., 2012).”
Estradiol regulates daily rhythms underlying diet-induced obesity in female mice
Omotola, O. B., Legan, S. J., Slade, E., Adekunle, A. D., & Pendergast, J. S. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00365.2019 · Cited by 44
“Recent studies in humans and rodents have revealed that the timing of behaviors, such as food intake, also affect energy balance and glucose homeostasis (1, 6, 7, 9, 14, 19, 22, 24, 47, 52, 53).”
BackgroundVelingkaar, N., Mezhnina, V., Poe, A., Makwana, K., Tulsian, R., & Kondratov, R. V. (2020) · Aging Cell · doi:10.1111/acel.13138 · Cited by 40
“Importantly, most TR studies were conducted in context of high-fat diet, obesity, or circadian rhythm disruption (Chaix et al., 2014; Hatori et al., 2012; Sherman et al., 2012).”
BackgroundTime restricted eating as a weight loss intervention in adults with obesity
Przulj, D., Ladmore, D., Smith, K. M., Phillips‐Waller, A., & Hájek, P. (2021) · PLoS ONE · doi:10.1371/journal.pone.0246186 · Cited by 43
Manipulating the Circadian and Sleep Cycles to Protect Against Metabolic Disease
Nohara, K., Yoo, S. H., & Chen, Z. (. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00035 · Cited by 43
de Goede, P., Foppen, E., Ritsema, W. I. G. R., Korpel, N. L., Yi, C., & Kalsbeek, A. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00554 · Cited by 41
“and insulin sensitivity for several different nutritional challenges, even when TRF was applied only during weekdays and not during the weekend (8).”
BackgroundCorreia, J. M., Santos, I., Pezarat‐Correia, P., Minderico, C. S., Schoenfeld, B. J., & Mendonça, G. V. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18147227 · Cited by 42
“Although significant decreases in FM with TRF have been reported in some previous studies [2,3,6], we were unable to replicate such findings.”
BackgroundResultThe hepatocyte insulin receptor is required to program the liver clock and rhythmic gene expression
Fougeray, T., Polizzi, A., Régnier, M., Fougerat, A., Ellero‐Simatos, S., Lippi, Y., Smati, S., Lasserre, F., Tramunt, B., Huillet, M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110674 · Cited by 40
Queiroz, J. D. N., Macedo, R. C. O., dos Santos, G. C., Munhoz, S. V., Machado, C. L. F., Leal-Menezes, R., Nascimento, E. M., Moritz, C. E. J., Pinto, R. S., Tinsley, G. M., et al. (2022) · British Journal Of Nutrition · doi:10.1017/s0007114522001581 · Cited by 42
“This approach, which aligns eating with the active biological phase, improves health outcomes in rodents – regardless of energy restriction, weight loss or diet quality(6,7).”
BackgroundObesity, cancer risk, and time-restricted eating
Das, M., & Webster, N. J. G. (2022) · Cancer and Metastasis Reviews · doi:10.1007/s10555-022-10061-3 · Cited by 43
The effects of time-restricted feeding on lipid metabolism and adiposity
Chaix, A., & Zarrinpar, A. (2015) · Adipocyte · doi:10.1080/21623945.2015.1025184 · Cited by 40
“Accordingly, adiponectin and leptin were increased and decreased, respectively, in TRF mice.(3,4) The observed decrease in fat was generalized to the whole body, affecting both canonical and non-canonical fat storing organs (e.”
BackgroundResultInfluentialWhen should I eat: A circadian view on food intake and metabolic regulation
Chamorro, R., Jouffe, C., Oster, H., Uhlenhaut, N. H., & Meyhöfer, S. M. (2023) · Acta Physiologica · doi:10.1111/apha.13936 · Cited by 40
Guerrero‐Vargas, N. N., Zárate‐Mozo, C., Guzmán‐Ruiz, M. A., Cárdenas‐Rivera, A., & Escobar, C. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24741 · Cited by 41
“TRF to the active period restored circadian rhythms and prevented obesity, hyperinsulinemia, and inflammation in mice fed a high fat diet (Chaix et al., 2014; Haraguchi et al., 2014; Hatori et al., 2012; Sundaram & Yan, 2016).”
BackgroundMethodGaining Insights into Diabetic Cardiomyopathy from Drosophila
Diop, S. B., & Bodmer, R. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.009 · Cited by 41
“The TRF mice also exhibited improved circadian rhythms, increased glucose tolerance, and decreased fatty acid levels, and they were protected from hepatic steatosis [54,55].”
Circadian rhythms and proteomics: It's all about posttranslational modifications!
Mauvoisin, D. (2019) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1450 · Cited by 40
Time-restricted feeding rescues high-fat-diet-induced hippocampal impairment
Davis, J. A., Paul, J. R., Yates, S. D., Cutts, E. J., McMahon, L. L., Pollock, J. S., Pollock, D. M., Bailey, S. M., & Gamble, K. L. (2021) · iScience · doi:10.1016/j.isci.2021.102532 · Cited by 38
“Mice provided an HFD on a TRF schedule do not gain as much weight or develop HFD-induced diabetes or liver damage (Hatori et al., 2012; Chung et al., 2016; Chaix et al., 2014).”
BackgroundMethodResultInfluentialCOVID-19 and obesity: fighting two pandemics with intermittent fasting
Ealey, K. N., Phillips, J. C., & Sung, H. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.06.004 · Cited by 41
“In mice consuming various obesogenic diets, limiting food access to 8–9 h during the active phase prevented body weight gain and fat accumulation, reversed pre-existing obesity and glucose intolerance, and reduced markers of adipose tissue inflammation in obese mice, regardless of diet and caloric intake [66].”
BackgroundWang, W., Wei, R., Pan, Q., & Guo, L. (2022) · Nutrition & Metabolism · doi:10.1186/s12986-022-00711-2 · Cited by 39
“[44, 45] showed that intermittent fasting improved myocardial ischemia-reperfusion injury and reduced circulating cholesterol and triglyceride levels.”
BackgroundDuregon, E., Fernández, M. E., Romero, J. M., Germanio, C. D., Cabassa, M., Voloshchuk, R. S., Ehrlich-Mora, M. R., Moats, J. M., Wong, S., Bosompra, O., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.05.003 · Cited by 36
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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