Timed high‐fat diet resets circadian metabolism and prevents obesity

May 18, 2012FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Eating a high-fat diet at set times resets body clock metabolism and helps prevent obesity

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Abstract

Timed high-fat diet feeding resulted in 18% lower body weight compared to ad libitum high-fat diet feeding.

Long-term timed feeding can reset the body's circadian clock and improve metabolic health.
Mice on a timed high-fat diet showed 30% decreased cholesterol levels compared to those on an unrestricted high-fat diet.
Insulin sensitivity was 3.7-fold improved in the timed high-fat diet group compared to the ad libitum high-fat diet group.
Mice on the timed high-fat diet exhibited 25% lower ghrelin and 53% lower corticosterone levels, indicating a less stressed phenotype.
The timed high-fat diet restored the expression phase of several clock genes linked to metabolism.

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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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Timed high‐fat diet resets circadian metabolism and prevents obesity

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