Timed high-fat diet resets circadian metabolism and prevents obesity

Sherman, Hadas; Genzer, Yoni; Cohen, Rotem; Chapnik, Nava; Madar, Zecharia; Froy, Oren

doi:10.1096/fj.12-208868

Cited by 360Circadian rhythm and melatoninDietary Effects on HealthRegulation of Appetite and Obesity

Timed high-fat diet resets circadian metabolism and prevents obesity

Sherman, Hadas, Genzer, Yoni, Cohen, Rotem, Chapnik, Nava, Madar, Zecharia, Froy, Oren·2012·The FASEB Journal

DOI 10.1096/fj.12-208868

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Abstract

Disruption of circadian rhythms leads to obesity and metabolic disorders. Timed restricted feeding (RF) provides a time cue and resets the circadian clock, leading to better health. In contrast, a high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. We tested whether long-term (18 wk) clock resetting by RF can attenuate the disruptive effects of diet-induced obesity. Analyses included liver clock gene expression, locomotor activity, blood glucose, metabolic markers, lipids, and hormones around the circadian cycle for a more accurate assessment. Compared with mice fed the HF diet ad libitum, the timed HF diet restored the expression phase of the clock genes Clock and Cry1 and phase-advanced Per1, Per2, Cry2, Bmal1, Rorα, and Rev-erbα. Although timed HF-diet-fed mice consumed the same amount of calories as ad libitum low-fat diet-fed mice, they showed 12% reduced body weight, 21% reduced cholesterol levels, and 1.4-fold increased insulin sensitivity. Compared with the HF diet ad libitum, the timed HF diet led to 18% lower body weight, 30% decreased cholesterol levels, 10% reduced TNF-α levels, and 3.7-fold improved insulin sensitivity. Timed HF-diet-fed mice exhibited a better satiated and less stressed phenotype of 25% lower ghrelin and 53% lower corticosterone levels compared with mice fed the timed low-fat diet. Taken together, our findings suggest that timing can prevent obesity and rectify the harmful effects of a HF diet.

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In mice, restricting feeding to the middle of the light or dark phase reduces body weight and improves markers of metabolic health compared with ad libitum feeding, despite equivalent calorie consumption.
“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 [84]

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doi:10.5402/2012/437198 Review Article Circadian Rhythms and Obesity in Mammals
Obesity, I., & Froy, O. (2012)
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Time restricted feeding attenuates metabolic dysregulation and demonstrates legacy effect in high fat diet rat model
Fatima, N., Sonkar, G. K., Singh, S., Sonkar, S. K., & Mahdi, A. A. (2026) · Indian Journal of Experimental Biology · doi:10.56042/ijeb.v64i01.20696

Authors: Sherman, H., Genzer, Y., Cohen, R., Chapnik, N., Madar, Z., & Froy, O.
Affiliations: Hebrew University of Jerusalem (IL)
Corresponding author: Froy, Oren
ORCID: Chapnik, Nava
Madar, Zecharia
Froy, Oren
Venue: The FASEB Journal
Publisher: Wiley
Published: 2012-05-16
Volume: 26
Issue: 8
Pages: 3493-3502
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.12-208868
OpenAlex: W2138503496
Cited by: 360
References: 40
Citations by year: 2026: 15 · 2025: 14 · 2024: 20 · 2023: 26 · 2022: 38 · 2021: 32 · 2020: 39 · 2019: 33 · 2018: 24 · 2017: 29 · 2016: 20 · 2015: 27 · 2014: 22 · 2013: 18 · 2012: 3
FWCI: 9.91
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Health Sciences › Medicine › Physiology › Dietary Effects on Health
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: high-fat diet, diet-induced obesity, circadian clock, clock gene expression, circadian metabolism, insulin sensitivity, cholesterol, ghrelin, corticosterone, TNF-α, locomotor activity, body weight
MeSH terms: Animals, Circadian Rhythm, Corticosterone, Diet, Eating, Insulin Resistance, Lipids, Male, Motor Activity, Mice, CLOCK Proteins, Diet, High-Fat

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Timed high-fat diet resets circadian metabolism and prevents obesity

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