Exposure to dim light at night alters daily rhythms of glucose and lipid metabolism in rats

Abstract

Nocturnal light pollution has been rapidly increasing during the last decades and even though dim artificial light at night (ALAN) has been associated with metabolic diseases, its mechanism is still far from clear. Therefore, the aim of our study was to thoroughly analyze the effects of ALAN on energy metabolism, metabolites, metabolic hormones, and gene expression. Male Wistar rats were kept in either the standard light:dark (12:12) cycle or exposed to ALAN (∼2 lx) during the whole 12-h dark phase for 2 weeks. Energy metabolism was measured in metabolic cages. In addition, we measured plasma and hepatic metabolites, clock and metabolic gene expression in the liver and epididymal adipose tissue, and plasma hormone levels. In ALAN rats, we observed an unexpected transitory daytime peak of locomotor activity and a suppression of the peak in locomotor activity at the beginning of the dark period. These changes were mirrored in the respiratory exchange ratio. Plasma metabolites became arrhythmic, and plasma and hepatic cholesterol levels were increased. Lost rhythmicity of metabolites was associated with disrupted behavioral rhythms and expression of metabolic genes. In the liver, the rhythms of metabolic sensors were either phase-advanced (Ppara, Pgc1a, Nampt) or arrhythmic (Sirt1, Lxra) after ALAN. The rhythmic pattern of Ppara and Sirt1 was abolished in the adipose tissue. In the liver, the amplitude of the daily rhythm in glycogen content was attenuated, the Glut2 rhythm was phase-advanced and Foxo1 lost its daily rhythmicity. Moreover, hepatic Foxo1 and Gck were up-regulated after ALAN. Interestingly, several parameters of lipid metabolism gained rhythmicity (adiponectin, Hmgcs2, Lpl, Srebf1c) in the liver, whereas Noct became arrhythmic in the adipose tissue. Peripheral clock genes maintained their robust oscillations with small shifts in their acrophases. Our data show that even a low level of ALAN can induce changes in the daily pattern of behavior and energy metabolism, and disturb daily rhythms of genes encoding key metabolic sensors and components of metabolic pathways in the liver and adipose tissue. Disturbed metabolic rhythms by ALAN could represent a serious risk factor for the development and progression of metabolic diseases.

Artificial Dim Light at Night during Pregnancy Can Affect Hormonal and Metabolic Rhythms in Rat Offspring

“…This difference between groups is most likely determined predominantly by mothers. In our recent study with mature male rats [ 14 ], the same intensity of ALAN eliminated daily oscillations of plasma metabolites in the ALAN but not in the CTRL group. To our knowledge, no studies dealing with the rhythmicity of hormones and metabolites in pregnant females exposed to ALAN are available, requiring further research.…”

“…However, recent studies suggest that a low intensity of ALAN lasting all night can interfere with vital physiological [ 11 ] and neural processes in humans [ 12 ]. Molecular mechanisms mediating the negative effects of ALAN are explored in animal experiments and include disruption of the circadian rhythms in metabolism [ 13 , 14 ], sleep [ 15 ], or the immune system [ 16 , 17 ]. The developmental aspects of chronodisruption have been less studied compared to mature animals and humans but can be important because maternal shift work can have negative consequences for offspring [ 18 ].…”

“…Our recent study in laboratory rats demonstrates that even dim ALAN (~2 lx), which can be commonly found in cities, disturbs the rhythmic expression of clock and clock-controlled genes in the SCN, eliminates the daily rhythms of plasma melatonin and testosterone, and vasopressin and disturbs the daily corticosterone rhythm [ 35 ]. Moreover, the daily rhythms of key metabolites and metabolic sensors were disturbed in mature male rats kept under identical lighting conditions [ 14 ]. It is unknown if such a level of dim ALAN during pregnancy can affect the development of daily rhythms in key hormonal and metabolic signals.…”

Circadian Disruption and Consequences on Innate Immunity and Inflammatory Response

“…Evidence provided by experimental studies has demonstrated that dim ALAN (≤5 lx) can compromise circadian coordination in laboratory rodents. The rhythmic profile of locomotor activity was preserved in rats exposed to dim ALAN for 2 weeks, but mean night-time levels were reduced, and daytime activity was increased compared to controls [ 127 ]. Another study in rats reported that dim ALAN diminished the power of 24 h activity rhythm and induced a second approximately 25 h free-running rhythm, indicating internal desynchronization of locomotor activity [ 128 ].…”

“…In the SCN, dim ALAN exposure clearly suppressed the daily rhythms of clock genes in both rats [ 129 , 130 ] and mice [ 131 , 132 ]. In peripheral tissues, clock gene rhythms appeared to be less affected by ALAN than in the master oscillator, though they showed lowered amplitude or shifts in acrophase [ 127 , 129 , 131 ]. The daily plasma melatonin rhythm was eliminated in rats after 2 weeks of dim ALAN (2 lx) exposure due to suppressed nocturnal melatonin levels [ 129 ], which were also reported in other studies, not only in rats [ 133 , 134 ] but also in diurnal birds [ 135 , 136 ] and humans [ 137 ].…”