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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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“…feeding without caloric restriction synchronizes diet-induced rhythms with the central circadian pacemaker, thereby amplifying circadian and metabolic cycles, which may produce long-term effects to prevent obesity and its metabolic consequences (Chaix et al., 2014; Hatori et al., 2012).”
BackgroundPARPs in lipid metabolism and related diseases
Szántó, M., Gupte, R., Kraus, W. L., Pacher, P., & Bai, P. (2021) · Progress in Lipid Research · doi:10.1016/j.plipres.2021.101117 · Cited by 181
Manoogian, E. N. C., Zadourian, A., Lo, H. C., Gutierrez, N. R., Shoghi, A., Rosander, A. M., Pazargadi, A., Ormiston, C. K., Wang, X., Sui, J., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.08.018 · Cited by 191
Disturbances of sleep and circadian rhythms: novel risk factors for obesity
Broussard, J. L., & Cauter, E. V. (2016) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000276 · Cited by 183
Prolonged Nightly Fasting and Breast Cancer Prognosis
Marinac, C. R., Nelson, S. H., Breen, C. I., Hartman, S. J., Natarajan, L., Pierce, J. P., Flatt, S. W., Sears, D. D., & Patterson, R. E. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.0164 · Cited by 187
Huang, S., Chen, J., Cui, Z., Ma, K., Wu, D., Luo, J., Li, F., Xiong, W., Rao, S., Xiang, Q., et al. (2023) · Science Advances · doi:10.1126/sciadv.adi7337 · Cited by 186
“(iii) Obesity in mice can be inhibited by homeostasis in circadian eating rhythms independent of energy intake ( 59 , 60 ).”
Jakubowicz, D., Wainstein, J., Landau, Z., Raz, I., Ahren, B., Chapnik, N., Ganz, T., Menaged, M., Barnea, M., Bar-Dayan, Y., et al. (2017) · Diabetes Care · doi:10.2337/dc16-2753 · Cited by 178
Circadian metabolism in the light of evolution
Gerhart-Hines, Z., & Lazar, M. A. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1007 · Cited by 178
Skene, D. J., Skornyakov, E., Chowdhury, N. R., Gajula, R. P., Middleton, B., Satterfield, B. C., Porter, K. I., Van Dongen, H. P. A., & Gaddameedhi, S. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1801183115 · Cited by 176
“Time-restricted feeding patterns also affect the mouse metabolome (43), but the phase shifting in peripheral oscillators appears to be independent of clock gene expression in the central SCN pacemaker (17, 42).”
BackgroundIntersection of the Gut Microbiome and Circadian Rhythms in Metabolism
Frazier, K., & Chang, E. B. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.08.013 · Cited by 171
Dietary restriction with and without caloric restriction for healthy aging
Lee, C. D., & Longo, V. D. (2016) · F1000Research · doi:10.12688/f1000research.7136.1 · Cited by 178
“Ad lib feeding during the weekend did not interfere with the protective effects of time-restricted feeding 52 .”
BackgroundInfluentialPak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., Yang, S. E., Dumas, S. N., Sonsalla, M., Bray, L., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00466-9 · Cited by 171
Circadian Rhythms in the Pathogenesis and Treatment of Fatty Liver Disease
Saran, A., Dave, S., & Zarrinpar, A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.050 · Cited by 179
Collado, M. C., Engen, P. A., Bandín, C., Cabrera‐Rubio, R., Voigt, R. M., Green, S. J., Naqib, A., Keshavarzian, A., Scheer, F. A. J. L., & Garaulet, M. (2018) · The FASEB Journal · doi:10.1096/fj.201700697rr · Cited by 168
Pellegrini, M., Cioffi, I., Evangelista, A., Ponzo, V., Goitre, I., Ciccone, G., Ghigo, E., & Bo, S. (2020) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09524-w · Cited by 168
Greenwell, B. J., Trott, A. J., Beytebiere, J. R., Pao, S., Bosley, A. M., Beach, E., Finegan, P., Hernandez, C., & Menet, J. S. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.064 · Cited by 168
“Experiments using temporal-restricted feeding paradigms demonstrated that the daily rhythm of food intake is a major synchronizing cue for the circadian clock and circadian transcriptional programs in the liver and other peripheral tissues (Chaix et al., 2014; Damiola et al., 2000; Hatori et al., 2012; Kawamoto et al.…”
BackgroundCircadian Rhythms, Disease and Chronotherapy
Lee, Y., Field, J. M., & Sehgal, A. (2021) · Journal of Biological Rhythms · doi:10.1177/07487304211044301 · Cited by 185
“…phase improves internal clock rhythms and metabolic health indices compromised by high-fat diets, thus relieving or reversing metabolic conditions associated with obesity, diabetes mellitus type 2, hyperlipidemia, fatty liver disease, and inflammation (Hatori et al., 2012; Chaix et al., 2014).”
BackgroundInterconnections between circadian clocks and metabolism
Guan, D., & Lazar, M. A. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148278 · Cited by 173
60 years of healthy aging: On definitions, biomarkers, scores and challenges
Behr, L. C., Simm, A., Kluttig, A., & Großkopf, A. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101934 · Cited by 184
“inflammation and supported defense mechanisms against reactive oxygen species (Chaix et al., 2014).”
Parr, E. B., Devlin, B. L., Radford, B. E., & Hawley, J. A. (2020) · Nutrients · doi:10.3390/nu12020505 · Cited by 169
“In rodents, adherence to a TRF eating pattern only on weekdays still had a positive effect on weight loss [9,37] and, whilst similar studies need to take place in humans, reducing TRF to five of the seven days of the week may improve adherence to a TRF dietary pattern.”
BackgroundLipid metabolism around the body clocks
Petrenko, V., Sinturel, F., Riezman, H., & Dibner, C. (2023) · Progress in Lipid Research · doi:10.1016/j.plipres.2023.101235 · Cited by 171
Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
Hwangbo, D., Lee, H., Abozaid, L. S., & Min, K. (2020) · Nutrients · doi:10.3390/nu12041194 · Cited by 173
Circadian clocks in the digestive system
Segers, A., & Depoortere, I. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00401-5 · Cited by 165
The circadian coordination of cell biology
Chaix, A., Zarrinpar, A., & Panda, S. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201603076 · Cited by 159
“Additionally, using behavioral modifications that can counteract the clock dampening, like time-restricted feeding, can prevent and reverse metabolic diseases in mice (Hatori et al., 2012; Chaix et al., 2014).”
MethodSelf-citationTime‐restricted feeding for prevention and treatment of cardiometabolic disorders
Melkani, G. C., & Panda, S. (2017) · The Journal of Physiology · doi:10.1113/jp273094 · Cited by 155
“In Drosophila TRF also exerts beneficial cardiometabolic effects, thus illustrating the relevance of eating pattern on metabolic health across species (Hatori et al. 2012; Sherman et al. 2012; Chaix et al. 2014, 2016; Panda, 2016; Zarrinpar et al. 2016).”
InfluentialSelf-citationMcAllister, M. J., Pigg, B., Rentería, L. I., & Waldman, H. S. (2019) · Nutrition Research · doi:10.1016/j.nutres.2019.12.001 · Cited by 152
“Most of the data showing cardiometabolic benefits of TRF are coming from rodent models utilizing isocaloric TRF [23, 29-31]; however, mice following ad libitum high fat, energy dense diets are protected against obesity and metabolic disease when following a TRF protocol [31].”
BackgroundMethodAntoni, R., Robertson, T. M., Robertson, M. D., & Johnston, J. D. (2018) · Journal of Nutritional Science · doi:10.1017/jns.2018.13 · Cited by 154
“Beneficial effects of TRF schedules on murine body weight can occur within 8 weeks; lower fat mass and serum cholesterol, together with improved glucose tolerance, occur by the end of a 9-week protocol using a daily 15 h window of food availability((6)).”
BackgroundChrono-nutrition for the prevention and treatment of obesity and type 2 diabetes: from mice to men
Hawley, J. A., Sassone‐Corsi, P., & Zierath, J. R. (2020) · Diabetologia · doi:10.1007/s00125-020-05238-w · Cited by 159
“A feature common to these dietary interventions is the manipulation of the feeding–fasting cycle, along with the assumption that reducing the time spent in a postprandial and postabsorptive state improves glycaemic control, and that perturbing feeding–fasting cycles drive robust oscillations in metabolism and circadia…”
BackgroundWhittaker, D. S., Akhmetova, L., Carlin, D., Romero, H., Welsh, D. K., Colwell, C. S., & Desplats, P. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.07.014 · Cited by 147
Chrono-Nutrition: Circadian Rhythm and Personalized Nutrition
Franzago, M., Alessandrelli, E., Notarangelo, S., Stuppia, L., & Vitacolonna, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032571 · Cited by 183
“In FTR, the daily eating duration, that is, the time between the first and last energy intake, is typically reduced from a 12–14 h day to <10 h day [8,55,57,58].”
BackgroundVillanueva, J. E., Livelo, C., Trujillo, A. S., Chandran, S., Woodworth, B., Andrade, L., Le, H. D., Manor, U., Panda, S., & Melkani, G. C. (2019) · Nature Communications · doi:10.1038/s41467-019-10563-9 · Cited by 160
Chung, H., Chou, W., Sears, D. D., Patterson, R. E., Webster, N. J. G., & Ellies, L. G. (2016) · Metabolism · doi:10.1016/j.metabol.2016.09.006 · Cited by 149
“Recent studies show that a prolonged daily fast (> 12 h) occurring predominantly during the inactive or sleeping phase, without calorie restriction is sufficient to prevent obesity and insulin resistance in male mice [23, 36].”
Background
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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