Chronobiology and obesity: Interactions between circadian rhythms and energy regulation

Abstract

Recent advances in the understanding of the molecular, genetic, neural, and physiologic basis for the generation and organization of circadian clocks in mammals have revealed profound bidirectional interactions between the circadian clock system and pathways critical for the regulation of metabolism and energy balance. The discovery that mice harboring a mutation in the core circadian gene circadian locomotor output cycles kaput (Clock) develop obesity and evidence of the metabolic syndrome represented a seminal moment for the field, clearly establishing a link between circadian rhythms, energy balance, and metabolism at the genetic level. Subsequent studies have characterized in great detail the depth and magnitude of the circadian clock's crucial role in regulating body weight and other metabolic processes. Dietary nutrients have been shown to influence circadian rhythms at both molecular and behavioral levels; and many nuclear hormone receptors, which bind nutrients as well as other circulating ligands, have been observed to exhibit robust circadian rhythms of expression in peripheral metabolic tissues. Furthermore, the daily timing of food intake has itself been shown to affect body weight regulation in mammals, likely through, at least in part, regulation of the temporal expression patterns of metabolic genes. Taken together, these and other related findings have transformed our understanding of the important role of time, on a 24-h scale, in the complex physiologic processes of energy balance and coordinated regulation of metabolism. This research has implications for human metabolic disease and may provide unique and novel insights into the development of new therapeutic strategies to control and combat the epidemic of obesity.

Conflict of interest statement

Author disclosures: K. C. Summa and F. W. Turek, no conflicts of interest.

© 2014 American Society for Nutrition.

Figures

FIGURE 1

A high-fat (HF) diet lengthens the circadian period in mice. Young adult, male, wild-type C57BL/6J mice were fed unpurified diet [regular chow (RC)] (A) or an HF diet (B) and released from entrained light:dark (LD) conditions to constant darkness (DD). Four representative activity records of individual mice are shown for each experimental group. (C) Comparison of free-running period (i.e., the length of time between the onset of activity of successive activity bouts) over time between mice fed RC (black bars; n = 12) and an HF diet (gray bars; n = 10). Week 0 represents the LD condition when all mice were fed RC. Week 1 is the first week being fed the respective experimental diet. (D) Distribution of free-running periods in mice fed RC or an HF after 6 wk being fed the diet. Values in panel C are means + SEMs. *P < 0.05. Reproduced from reference with permission.

FIGURE 2

Light-phase feeding leads to increased weight gain in mice fed a high-fat diet. (A) Young adult, male, wild-type C57BL/6J mice were fed a high-fat diet exclusively during the dark phase (solid lines) or light phase (dashed lines) for 6 wk. Body weights were recorded weekly. Mice fed during the light phase (i.e., the “wrong” time of day for nocturnal mice) gained significantly more weight than did mice fed during the dark phase (*P < 0.05). (B) There were no significant differences in locomotor activity levels or food intake between the experimental groups. Values in panels A and B are means ± SEMs. Reproduced from reference with permission.