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

Abstract

Light pollution worldwide promotes the progression of obesity, which is widely considered a consequence of circadian rhythm disruptions. However, the role of environmental light wavelength in mammalian obesity is not fully understood. Herein, mice fed a normal chow diet (NCD) or a high-fat diet (HFD) were exposed to daytime white (WL), blue (BL), green (GL), and red light (RL) for 8 weeks. Compared with WL and RL, BL significantly increased weight gain and white adipose tissue (WAT) weight, and it disrupted glucose homeostasis in mice fed with HFD but not NCD. The analysis of WAT found that BL significantly aggravated HFD-induced WAT hypertrophy, with a decrease in IL-10 and an increase in NLRP3, p-P65, p-IκB, TLR4, Cd36, Chrebp, Srebp-1c, Fasn, and Cpt1β relative to WL or RL. More interestingly, BL upregulated the expression of circadian clocks in the WAT, including Clock, Bmal1, Per1, Cry1, Cry2, Rorα, Rev-erbα, and Rev-erbβ compared with WL or RL. However, most of the changes had no statistical difference between BL and GL. Mechanistically, BL significantly increased plasma corticosterone (CORT) levels and glucocorticoid receptors in the WAT, which may account for the changes in circadian clocks. Further, in vitro study confirmed that CORT treatment did promote the expression of circadian clocks in 3T3-L1 cells, accompanied by an increase in Chrebp, Cd36, Hsp90, P23, NLRP3, and p-P65. Thus, daily BL, rather than RL exposure-induced CORT elevation, may drive changes in the WAT circadian clocks, ultimately exacerbating lipid dysmetabolism and adipocytic hypertrophy in the HFD-fed mice.

Keywords: adipose hypertrophy; circadian clocks; corticosterone; high-fat diet; monochromatic light pollution.

Figure 1

Influences of monochromatic light exposure on metabolic disorders in mice. (A) Schematic diagram of animal experiments. (B) Body weight gain (n = 7). (C–I) Weights of the heart, liver, spleen, kidney, Epi-WAT, Ing-WAT, and BAT (n = 7). (J,K) Plasma TC and TG concentrations (n = 5). (L) Fasting blood glucose level (n = 7). (M–O) GTT and ITT curve and relevant AUC (n = 7). The circles represent the number of samples. The results are presented as the means ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 2

Influences of monochromatic light exposure on WAT hypertrophy and inflammation in mice. (A) H&E staining of the Epi-WAT (scale: 50 μm). (B) Adipocyte density (n = 6). (C) Mean adipocyte size (n = 6). (D,E) Concentrations of IL-6 and IL-10 in the Epi-WAT (n = 6). (F–I) Relative protein expression levels of NLRP3, p-P65, p-IκB, and TLR4 in the Epi-WAT (n = 3). (J–N) Relative mRNA expression levels of Cd36, Chrebp, Srebp-1c, Fasn, and Cpt1β (n = 6). The circles represent the number of samples. The results are presented as the means ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 3

Influences of monochromatic light exposure on the expression of circadian genes in the WAT. (A–I) Relative mRNA expression levels of Clock, Bmal1, Per1, Per2, Cry1, Cry2, Rorα, Rev-erbα, and Rev-erbβ in the Epi-WAT (n = 6). (J,K) Relative protein expression levels of CLOCK and BMAL1 in the Epi-WAT (n = 3). The results are presented as the means ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 4

Influences of monochromatic light exposure on BAT whitening and expression of circadian genes in BAT. (A) H&E staining of BAT (scale: 50 μm). (B–G) Relative mRNA expression levels of genes involved in lipid metabolism in the BAT, including Ucp1, Ucp3, Pgc-1α, Cd36, Srebp-1c, Cpt1β (n = 6). (H–P) Relative mRNA expression levels of Clock, Bmal1, Per1, Per2, Cry1, Cry2, Rorα, Rev-erbα, and Rev-erbβ in the BAT (n = 3). The results are presented as the means ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 5

Influences of monochromatic light exposure on CORT concentrations. (A–C) Plasma concentrations of CORT, melatonin, and noradrenaline (n = 7). (D) Relative protein expression level of GR in the Epi-WAT (n = 3). (E–G) Relative mRNA expression levels of Hsp90, Hsp70, and P23 in the Epi-WAT (n = 6). The circles represent the number of samples. The results are presented as the means ± SEM. * p < 0.05.

Figure 6

The role of CORT in interference with the adipose circadian rhythms. (A) Cell viability (% of CON). (B–P) Relative mRNA expression levels of Clock, Bmal1, Per1, Per2, Cry1, Cry2, Rorα, Rev-erbα, Rev-erbβ, Chrebp, Srebp-1c, Cd36, Hsp70, Hsp90, and P23 in 3T3-L1 cells treated by CORT (n = 3). (Q–S) Relative protein levels of NLRP3 and p-P65 (n = 3). The circles represent the number of samples. The results are presented as the means ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 7

A schematic of our proposed model. Effects of long daytime monochromatic light exposure on adipose hypertrophy in mice fed with HFD. BL exposure increases the level of plasma CORT, which disturbs the circadian clocks in the WAT. Changes in circadian clocks may further regulate the process of lipid metabolism and ultimately lead to adipose hypertrophy. CORT, corticosterone; FA, fatty acid; HFD, high-fat diet; TG, triglyceride; WAT, white adipose tissue.