Timed high-fat diet resets circadian metabolism and prevents obesity

FASEB J. 2012 Aug;26(8):3493-502. doi: 10.1096/fj.12-208868. Epub 2012 May 16.

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.

MeSH terms

  • Animals
  • CLOCK Proteins
  • Circadian Rhythm / physiology*
  • Corticosterone / blood
  • Diet
  • Diet, High-Fat*
  • Eating
  • Insulin Resistance
  • Lipids / blood
  • Male
  • Mice
  • Motor Activity

Substances

  • Lipids
  • CLOCK Proteins
  • Corticosterone