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.

The emerging role of circadian rhythms in the development and function of thermogenic fat

“…For example, animals with a genetic circadian disruption, such as the mutation of CLOCK and the deletion of BMAL1, are prone to obesity and metabolic syndrome ( 38 – 40 ). Animals gained more weight under the altered light/dark cycle including shortened period and prolonged light as well as blue light ( 11 , 41 , 42 ). Behavioral misalignments, such as shift work, jet lag, and sleep disruption, can accelerate the occurrence and development of obesity and its associated metabolic disorders in both animal models and humans ( 7 , 43 – 45 ), in which the inactivation of thermogenic fat may be involved ( 11 , 13 , 46 , 47 ).…”

“…Many clock genes like Per1 and Per2 that contain GR-responsive elements can be regulated by glucocorticoids ( 93 ). Blue light increased the expression of circadian genes in the WAT partly by increasing plasma corticosterone ( 42 ). The constant light causes blunted corticosterone rhythm in mice ( 94 ).…”

Circadian Rhythms of Body Temperature and Locomotor Activity in Spontaneously Hypertensive Rats under Frequent Changes in Light Conditions

“…Nighttime light pollution, a modern urbanization phenomenon, contributes significantly to disrupting biorhythms [ 24 ]. It is worth noting that, in addition to the lighting regimen, the wavelength of light also influences changes in circadian rhythms, as demonstrated in studies involving monochromatic light [ 25 , 26 ].…”