Timed high‐fat diet resets circadian metabolism and prevents obesity

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.—Sherman, H., Genzer, Y., Cohen, R., Chapnik, N., Madar, Z., Froy, O. Timed high‐fat diet resets circadian metabolism and prevents obesity. FASEB J. 26, 3493–3502 (2012). www.fasebj.org