title: 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.
authors.affiliation: Institute of Biochemistry, Food Science, and Nutrition, Robert H. Smith Faculty of Agriculture, Food, and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Sherman
authors.forename: Yoni
authors.initials: Y
authors.lastname: Genzer
authors.forename: Rotem
authors.initials: R
authors.lastname: Cohen
authors.forename: Nava
authors.initials: N
authors.lastname: Chapnik
authors.forename: Zecharia
authors.initials: Z
authors.lastname: Madar
authors.forename: Oren
authors.initials: O
authors.lastname: Froy
mesh_terms: D000818:Animals; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D004032:Diet; D059305:Diet, High-Fat; D004435:Eating; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D009043:Motor Activity
chemical_list: D008055:Lipids; D056926:CLOCK Proteins; D003345:Corticosterone