Dim light at night disrupts molecular circadian rhythms and increases body weight

Abstract

With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption.

Keywords: clock genes; feeding rhythm; light pollution; obesity.

Figure 1

Mice exposed to light at night increased body mass. (A) Body mass in mice exposed to dimly lit and dark nights. (B) At the conclusions of the study body mass gain was increased among mice exposed to dim light at night as compared to dark nights. (C) Epididymal fat pad mass, an index of overall adiposity, was also increased in mice exposed to light at night. (D) Mice exposed to dim light at night altered timing of food intake consuming more during the light phase than mice exposed to dark nights. (E) There were no differences in blood glucose rhythms between lighting conditions. All data are presented as (mean ± SEM). *indicates dim light differs from dark nights.

Figure 2

Dim light at night attenuates the amplitude of clock gene expression in the hypothalamus and liver. Transcripts of the core circadian clock genes Clock, Bmal1, Per1, Per2, Cry1, and Cry2 were analyzed by quantitative PCR in the (A) hypothalamus (B) hippocampus, (C) white adipose tissue, and (D) liver. Tissues were collected every 4 hr from mice exposed to either dark (black lines) or dimly lit (dotted lines) nights for 4 weeks. Values are expressed as relative abundance (mean ± SEM) after normalization to 18S *indicates dim light differs from dark nights.

Figure 3

Dim light at night suppresses the amplitude of Rev-Erb mRNA expression in peripheral tissue. Rev-Erb gene expression was quantified in the (A) hypothalamus (B) hippocampus, (C) white adipose tissue, and (D) liver. Values are expressed as relative abundance (mean ± SEM) after normalization to 18S †indicates main effect of time, *indicates dim light differs from dark nights.

Figure 4

PER1 and PER2 protein expression are reduced in the suprachiasmatic nucleus of the hypothalamus of mice exposed to dimly lit as compared to dark nights. CLOCK, BMAL, PER1 and PER2 immunoreactivity were analyzed in hypothalamic tissue collected every 4 hr from mice exposed to either dark (black lines) or dimly lit (dotted lines) nights for 4 weeks. Images of sections containing the SCN were captured at 20X and the number of immonoreactive cells was counted and averaged across section and sides of the bilateral structure. Data are presented as (mean ± SEM). *indicates dim light differs from dark nights.