Timed high-fat diet resets circadian metabolism and prevents obesity.

Authors: Sherman H; Genzer Y; Cohen R; Chapnik N; Madar Z; Froy O

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, Roralpha, and Rev-erbalpha. 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-alpha 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.

Keywords: Animals; CLOCK Proteins; Circadian Rhythm/*physiology; Corticosterone/blood; Diet; *Diet, High-Fat; Eating; Insulin Resistance; Lipids/blood; Male; Mice; Motor Activity
Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume: 26
Issue: 8
Pages: 3493-502
Date: May 18, 2012
PMID: 22593546
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Categories: Circadian Rhythm
Citation:

Sherman H, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O (2012) Timed high-fat diet resets circadian metabolism and prevents obesity. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26: 3493-502.



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