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Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet
Open accessAbstract
While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.
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“Additionally, time-restricted feeding was found to compensate for the adverse effects of an unhealthy (high-fat) diet (57).”
From Meal timing and its role in obesity and associated diseases (2024) · cites this paper as [57]
In the citing paper
“Recent evidence from animal trials reported that eating at inappropriate circadian times may contribute to a poorer weight management and metabolic health [6,7,8].”
From Chronotype and Adherence to the Mediterranean Diet in Obesity: Results from the Opera Prevention Project (2020) · cites this paper as [7]
In the citing paper
“Studies in mice have reported beneficial effects of IF against diabetes and obesity with improvements in glucose tolerance and insulin sensitivity, maintenance of insulinemia within normal levels, and improvements in the phosphorylated cyclic AMP response element-binding protein (CREB), rapamycin complex (mTOR), and AMP-activated protein kinase (AMPK) pathways, even in mice fed high-fat diets [256”
From Effects of diet, lifestyle, Chrononutrition and alternative dietary interventions on postprandial Glycemia and insulin resistance (2022) · cites this paper as [336]
In the citing paper
“Restriction of feeding to either the middle of the light (84) or dark (42) phase reduces body weight and improves markers of metabolic health in mice compared with ad libitum fed controls.”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [42]
In the citing paper
“Of significance, mice that were fed a high-fat diet in a time-restricted manner, i.e. with regular fasting breaks, had lower inflammatory markers, no fatty liver and were slim in comparison to mice with equivalent total number of calories consumed ad libitum (Hatori et al., 2012).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Hatori et al., 2012
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Metadata
- Authors
- Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E. A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J. A. J., Ellisman, M. H., & Panda, S.
- Affiliations
- Salk Institute for Biological Studies (US)
- University of California San Diego (US)
- Corresponding author
- Panda, Satchidananda
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 15
- Issue
- 6
- Pages
- 848-860
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3491655
- OpenAlex
- W2123319274
- Cited by
- 1,986
- References
- 53
- Citations by year
- 2026: 131 · 2025: 159 · 2024: 158 · 2023: 179 · 2022: 202 · 2021: 203 · 2020: 226 · 2019: 139 · 2018: 123 · 2017: 116 · 2016: 101 · 2015: 89 · 2014: 83 · 2013: 55 · 2012: 18
- FWCI
- 52.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (P41GM103412)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32-DK07202, DK 091618, R01DK091618, T32DK007202)
- National Center for Research Resources (P41RR004050)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- time-restricted feeding, high-fat diet, diet-induced obesity, metabolic disorders, circadian clock, hepatic steatosis, hyperinsulinemia, inflammation, motor coordination, CREB, mTOR, AMPK, liver metabolome, energy expenditure
- MeSH terms
- Adenylate Kinase, Animals, Bile Acids and Salts, Adipose Tissue, Brown, Energy Intake, Cholesterol, Circadian Rhythm, Eating, Energy Metabolism, Fatty Liver, Glucose, Homeostasis, Liver, Male, Metabolic Diseases, Mice, Inbred C57BL, Oxygen Consumption, Phosphorylation, Time Factors, Weight Gain, Gene Expression, Cytokines, Cyclic AMP Response Element-Binding Protein, Ribosomal Protein S6 Kinases, Adiposity, Lipid Metabolism, Mice, Adipose Tissue, White, TOR Serine-Threonine Kinases, Diet, High-Fat
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