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Effect of early vs. late time-restricted high-fat feeding on circadian metabolism and weight loss in obese mice

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Abstract

Time-restricted feeding (TRF) limits the time and duration of food availability without calorie reduction. Although a high-fat (HF) diet leads to disrupted circadian rhythms, TRF can prevent metabolic diseases, emphasizing the importance of the timing component. However, the question of when to implement the feeding window and its metabolic effect remains unclear, specifically in obese and metabolically impaired animals. Our aim was to study the effect of early vs. late TRF-HF on diet-induced obese mice in an 8:16 light–dark cycle. C57BL male mice were fed ad libitum a high-fat diet for 14 weeks after which they were given the same food during the early (E-TRF-HF) or late (L-TRF-HF) 8 h of the dark phase for 5 weeks. The control groups were fed ad libitum either a high-fat (AL-HF) or a low-fat diet (AL-LF). Respiratory exchange ratio (RER) was highest for the AL-LF group and the lowest for the AL-HF group. E-TRF-HF led to lower body weight and fat depots, lower glucose, C-peptide, insulin, cholesterol, leptin, TNFα, and ALT levels compared with L-TRF-HF- and AL-HF-fed mice. TRF-HF regardless whether it was early or late led to reduced inflammation and fat accumulation compared with AL-HF-fed mice. E-TRF-HF led to advanced liver circadian rhythms with higher amplitudes and daily expression levels of clock proteins. In addition, TRF-HF led to improved metabolic state in muscle and adipose tissue. In summary, E-TRF-HF leads to increased insulin sensitivity and fat oxidation and decreased body weight, fat profile and inflammation contrary to AL-HF-fed, but comparable to AL-LF-fed mice. These results emphasize the importance of timed feeding compared to ad libitum feeding, specifically to the early hours of the activity period.

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Data availability

The data presented in this study are available on request from the corresponding author.

Abbreviations

ACC:

Acetyl CoA carboxylase

AL:

Ad libitum

AMPK:

AMP-activated protein kinase

DD:

Constant dark

FAS:

Fatty acid synthase

HDL:

High-density lipoprotein

HF:

High fat

HOMA-IR:

Homeostasis model assessment of insulin resistance

LD:

Light–dark

LDL:

Low-density lipoprotein

LF:

Low-fat

PPARα:

Peroxisome proliferator-activated receptor α

TG:

Triglycerides

TNFα:

Tumor necrosis factor α

TRF:

Time-restricted feeding

ZT:

Zeitgeber Time

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Acknowledgements

We would like to thank Dr. Ofer Gover and Barel Mishal for their assistance with the Metabolic System and Dr. Zohar Gavish at Gavish Research Services for the histology work.

Funding

This research was funded by the Israel Science Foundation (grant no. 1675/19). Shani Tsameret is a fellow of the Ariane de Rothschild Women Doctoral Program.

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Authors and Affiliations

  1. Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 76100, Rehovot, Israel

    Shani Tsameret, Nava Chapnik & Oren Froy

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  1. Shani Tsameret
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  2. Nava Chapnik
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  3. Oren Froy
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Contributions

Conceptualization, OF and ST; methodology, ST and NC; validation, OF, ST, and NC; formal analysis, ST; investigation, ST and NC; resources, OF; data curation, ST and NC; writing—original draft preparation, ST; writing—review and editing, OF; supervision, OF; funding acquisition, OF. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Oren Froy.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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The animal study was reviewed and approved by the joint ethics committee (IACUC) of the Hebrew University and Hadassah Medical Center.

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Tsameret, S., Chapnik, N. & Froy, O. Effect of early vs. late time-restricted high-fat feeding on circadian metabolism and weight loss in obese mice. Cell. Mol. Life Sci. 80, 180 (2023). https://doi.org/10.1007/s00018-023-04834-4

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