Effect of nighttime light exposure on glucose metabolism in protein-restricted mice

Abstract

Disruption of biological rhythms due exposure to artificial light at night (ALAN) has been emerged as new risk factor for metabolic diseases. However, it remains largely unexplored the effects induced by exposure to ALAN on energy metabolism with concomitant misalignment in the circadian system caused by nutritional imbalance. Objective: Here we evaluate whether low-protein diet could enhance the effects induced by exposure to ALAN on the energy metabolism and consequently predispose to metabolic disorders. Male C57BL6/J mice were weaned on a normal protein (NP) or a low-protein (LP) diet and housed on 12h light/dark (L/D) cycle. After 6 weeks, mice maintained on their respective diets were subdivided into normal light/dark cycle or exposed to ALAN for 8 weeks. We observed that exposure to ALAN concomitant to LP diet disrupts the behavioral rhythms, without shifting the timing of food intake. Furthermore, exposure to ALAN lead to increased body and fat pad weights, higher levels of fast and fed glycemia and glucose intolerance independent of the diet consumed. Importantly the insulin resistance developed in mice exposed to ALAN was diet-dependent. At the molecular level, exposure to ALAN concurrent with LP diet increased the expression of Phosphoenolpyruvate carboxykinase 1 in both periods analyzed and inverted the pattern of Fibroblast growth factor 21 (Fgf21) expression in the liver. Our data suggest that dietary protein restriction modulates the effects induced by nighttime light exposure on glucose metabolism, which could be partially related with the dysregulation on hepatic Fgf21 expression.

Circadian desynchrony and glucose metabolism

“…Light pollution at night not only affects the normal behavioral rhythms of animals, but also carries implications for human health 65 . In constant light conditions in the laboratory, mice become insulin resistant and have increased fasting glucose levels, 66‐68 but also short light pulses at night acutely impair glucose tolerance in rats and male diurnal grass rats 69‐71 and alter the liver transcriptome 72 . Dim light conditions at night (~2–5 lux) alter the daily rhythm of blood glucose concentrations, phase advance Glut2 expression in hepatocytes, and suppress rhythmicity of SCN clock genes in rats, 73,74 but do not seem to affect glucose tolerance 75 .…”

Circadian Regulation of Endocrine Fibroblast Growth Factors on Systemic Energy Metabolism

“…Environmental and behavioral stressors including changes in lighting conditions, sleep/wake and feeding/fasting patterns have been identified to cause circadian disruption of Fgf21 expression in rodents, an indicator of metabolic desynchrony. Exposure to artificial light at night with protein restriction feeding disturbed circadian glucose metabolism shown as the inversed circadian pattern of hepatic Fgf21 expression in mice (Borck et al, 2022). Nutrient redundancy in mice caused circadian disruption of molecular clocks presented as circadian dysregulation of CG expressions and nuclear receptor network, which directly or indirectly disturb the circadian expression of CCGs and circadian regulatory genes (Kohsaka et al, 2007).…”

Monochromatic Light Pollution Exacerbates High-Fat Diet-Induced Adipocytic Hypertrophy in Mice

“…Interestingly, the influence of light pollution on metabolic homeostasis has raised increasing attention in recent years [ 3 ]. Irregular light exposure has been proven to be a hazardous factor for obesity [ 4 , 5 , 6 ], as it promotes hepatic steatosis [ 7 , 8 ], increases fasting blood glucose (FBG), and induces insulin resistance (IR) [ 9 , 10 ]. The effects of ambient light exposure on metabolic homeostasis depend on light period, intensity, and wavelengths [ 11 ].…”