Effect Of LED Light-induced Circadian Disruption On Glucose And Lipid Metabolism In Mice

Objective:The circadian rhythm is a rhythmic life activity with a 24-hour cycle evolved by organisms to adapt to the changes in the light-dark cycles produced by the rotation of the earth.The progress of modern civilization makes people’s production and life highly dependent on artificial lighting,especially light-emitting diode(LED).Artificial light tends to cause circadian disruption due to lack of rhythmic changes of light intensity,spectrum,and photoperiod.Long-term circadian disruption induced by artificial light can cause glucose and lipid metabolic disorders,but its dose-effect relationship is still unclear.Therefore,this study carried out research on the influence of the three main light parameters of LED(light intensity,spectrum,photoperiod)on circ adian rhythm and glucose and lipid metabolism in mice.,aiming at revealing the characteristics of light-induced glucose and lipid metabolic disorders and providing a theoretical basis for designing lighting scheme in line with human circadian rhythm.Methods:(1)The effect of LED light intensity and spectrum on the circadian rhythm of mice:First,10-week-old male C57BL/6J mice were acclimated to a 25μW/cm~2-LED white light environment(light on at 8:00 and light off at 20:00)for 2 weeks.Then the mice were randomly divided into 12 groups(n=7)according to different spectra(380～750 nm white light,629 nm red light,533 nm green light,471 nm blue light)and light intensit ies(25,50,120μW/cm~2).At the same time,the light-dark cycles were advanced by 6 h(light on at2:00 and light off at 14:00),and then the Clock Lab data acquisition system was used to record the wheel-running activity of the mice for 2 weeks and Clock Lab analysis software was used to analyze the resynchronization speed,amplitude,and period of the rest-activity rhythm to evaluate the effect of light parameters on circadian rhythm.The rate of resynchronization was used to screen light parameters for subsequent studies of glucose and lipid metabolism,and the amplitude and period indicators were used to preliminarily evaluate the effect of the selected light parameters on circadian rhythmicity.(2)The effect of LED light intensity and light-dark cycle on glucose and lipid metabolism in mice:First,eighty 8-week-old male C57BL/6J mice were acclimated for 2weeks,and then were randomly divided into 8 groups(n=8～12)according to the different light intensities(25 and 50μW/cm~2),light-dark cycles(normal and jet-lag group),and diets(low-fat and high-fat).The light-dark cycle in normal group was 12h light:12h dark(light on at 8:00 and light off at 20:00),while the light-dark cycles in jet-lag group were 6-h phase advanced every 2 to 3 days.The light sources were white LEDs.During the experiment,the weight and diet amount of the mice were monitored for 14 weeks.Then,the light-dark cycle of the jet-lag group was restored to the normal light-dark cycle for 1 to 2 weeks,and the glucose and lipid metabolism parameters such as GTT and ITT were measured.(3)The effect of LED spectrum on glucose and lipid metabolism in mice under aberrant light-dark cycles:First,forty 6-week-old male C57BL/6J mice were acclimated for2 weeks,and then were randomly divided into 5 groups(n=8):control group,white light jet-lag group,629 nm red light jet-lag group,533 nm green light jet-lag group and 471 nm blue light jet-lag group.The control mice were exposed to white light(light on at 8:00 and light off at 20:00),while the lights were turned off 8-h earlier every Monday and 8-h delayed every Thursday in the jet lag group.The light intensities were 120μW/cm2.The mice were fed with high-fat diet.During the experiment,the weight and diet amount of the mice were monitored for 13 weeks.Then,the light-dark cycle of the jet-lag group was restored to the normal light-dark cycle for 1 to 2 weeks,and the glucose and lipid metabolism parameters such as GTT and ITT were measured.Results:(1)The effect of LED light intensity and spectrum on the circadian rhythm of mice:(1)The effect of light intensity on the resynchronization speed of the rest-activity rhythm of mice showed the same trend under white light,red light,and green light:25<120<50μW/cm~2 group,while the rate of resynchronization under blue light is 25<120=50μW/cm~2 group.(2)The effect of the spectrum on the resynchronization speed of the rest-activity rhythm of mice showed the same trent under different light intensities:red light<white light<green light=blue light group.(3)The white light intensity(25 and 50μW/cm~2)has no significant effect on the amplitude and period of the rest-activity rhythm in mice.Compared with white,green,and blue light,red light significantly redu ced the amplitude and shorten the period of the rest-activity rhythm of mice.(2)The effect of LED light intensity and light-dark cycle on glucose and lipid metabolism in mice:(1)On the low-fat diet regimen,compared with the normal light-dark cycle groups,the25μW/cm~2 abnormal light-dark cycle had no significant effect on the glucose and lipid metabolism of the mice,while the 50μW/cm~2 abnormal light-dark cycle significantly increased the body weight of mice,enlarged the epididymal adipocyte,impaired glucose tolerance,and increased insulin resistance.(2)On the high-fat diet regimen,compared with the normal light-dark cycle groups,the 25μW/cm~2 abnormal light-dark cycle reduced the body weight,the area of epididymal adipocyte,and insulin resistance of mice,while the 50μW/cm~2 abnormal light-dark cycle significantly increased the body weight of mice,increased the epididymal fat mass,enlarged the epididymal adipocyte,impaired glucose tolerance,and increased insulin resistance.(3)The effect of LED spectrum on glucose and lipid metabolism in mice under aberrant light-dark cycles:(1)The body weight of mice were significantly increased by white light and showed a decrease with shorter wavelength under other narrow-band spectra.(2)In terms of lipid metabolism,red light increased the epididymal fat mass,enlarged the epididymal adipocyte and increased the serum cholesterol level;green light aggravated fatty liver;blue light prevented mice from fatty liver and impaired liver function.(3)In terms of glucose metabolism,white light increased glucose intolerance,insulin resistance,andβ-cell mass.The fasting serum glucose level andβ-cell mass showed a decrease with shorter wavelength under other narrow-band spectra.Conclusion:(1)The resynchronization rate of rest-activity rhythm in mice showed a trend of"accelerating first and then slowing down with the increase of light intensity"and"accelerating with the shortening of wavelength".(2)Aberrant light-dark cycle with higher light intensity can impair glycolipid metabolism in mice under low and high fat diets.(3)The damage of aberrant light-dark cycle to glucose and lipid metabolism in mice tended to decrease with wavelength shortening.