Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 May 26;112(21):6748-53.
doi: 10.1073/pnas.1504239112. Epub 2015 May 11.

Prolonged Daily Light Exposure Increases Body Fat Mass Through Attenuation of Brown Adipose Tissue Activity

Affiliations
Free PMC article

Prolonged Daily Light Exposure Increases Body Fat Mass Through Attenuation of Brown Adipose Tissue Activity

Sander Kooijman et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity.

Keywords: brown adipose tissue; circadian rhythms; light pollution; obesity; triglyceride metabolism.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Mice were exposed to either 12-, 16-, or 24-h light (n = 9) for 5 wk, and body weight (A), lean mass (B), and fat mass (C) were determined. Correlations are depicted between the light-exposure period and total fat mass (D), gWAT weight (E), and adipocyte size in gWAT (G). Representative images of gWAT stained with H&E are shown (F). Food intake of the last 2 wk of light intervention was measured (H). Data are presented as means ± SEM. Dotted lines represent 95% confidence interval of the regression line. **P < 0.01.
Fig. 2.
Fig. 2.
Mice were exposed to either 12-, 16-, or 24-h light (n = 8–9) for 5 wk, and the VLDL-TG and glucose kinetics were assessed by injection of glycerol tri[3H]oleate ([3H]TO)-labeled emulsion particles and [14C]deoxyglucose ([14C]DG). Uptake of [3H]TO-derived activity by the various organs was determined (A), and correlations were determined between light exposure and [3H]TO-derived activity in iBAT (B), sBAT (C), and pVAT (D). Concomitantly, the uptake of [14C]DG by the various organs was determined (E), and correlations were determined between light exposure and the uptake of [14C]DG by iBAT (F), sBAT (G), and pVAT (H). Data are presented as means ± SEM. Dotted lines represent 95% confidence interval of the regression line.*P < 0.05, **P < 0.01, ***P < 0.001. Abbreviations of organs: iBAT, interscapular BAT; gWAT, gonadal WAT; pVAT, perivascular adipose tissue; sBAT, subscapular BAT; sWAT, subcutaneous WAT; vWAT, visceral WAT.
Fig. 3.
Fig. 3.
Mice were exposed to either 12-, 16-, or 24-h light (n = 9) for 5 wk, and iBAT was isolated. Histological sections were stained for TH, representative images are shown (A; arrows indicate TH staining), and quantified (B). Correlation was determined between TH staining and uptake of [3H]TO-derived activity (C) and [14C]DG (D). Additionally, correlations were determined between light exposure and protein levels of pCREB (E), pAMPK (F), and pHSL S565 (G). Protein levels were normalized to β-actin levels. Representative blots for β-actin, pCREB, pAMPK, and pHSL S565 are shown (H). Gene expression of Pgc1α (I) and Ucp1 (J) were determined and normalized to 36B4 expression. Data are presented as means ± SEM. Dotted lines represent 95% confidence interval of the regression line. *P < 0.05.
Fig. 4.
Fig. 4.
Mice underwent bilateral sympathetic denervation of iBAT or sham surgery. Denervated mice were exposed to either 12-, 16-, or 24-h light (n = 5–6) while sham mice were exposed to 12-h light exposure (n = 6). After 5 wk, iBAT was isolated and histologically stained for TH. Representative images are shown (A). Total food intake (B), locomotor activity (C), body weight gain (D), and fat mass gain (E) were determined. VLDL-TG and glucose kinetics were assessed by injection of glycerol tri[3H]oleate ([3H]TO)-labeled emulsion particles and [14C]deoxyglucose ([14C]DG). Uptake of [3H]TO-derived and [14C]DG activity by sBAT (F and G) and by iBAT was determined (H and I). Data are presented as means ± SEM; ns. = not significant, *P < 0.05, **P < 0.01, ***P < 0.001.
Fig. 5.
Fig. 5.
Proposed model on how light exposure modulates body fat mass through BAT activity. Daily light-exposure duration is perceived by the suprachiasmatic nucleus, which signals toward BAT via the sympathetic nervous system. At normal day length uptake of nutrients by BAT and WAT is in balance, whereas increasing daily light exposure result in reduced BAT activation and subsequent storage of excess energy in WAT. The decrease in noradrenaline (NA) availability for stimulation of the β3-adrenergic receptor (B3-AR) leads to: (i) reduced phosphorylation of CREB, which decreases transcription of UCP1; (ii) reduced phosphorylation of AMPK, resulting in decreased phosphorylation of HSL and thus decreased lipolysis.

Similar articles

See all similar articles

Cited by 27 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback