EFFECTS OF TIME- RESTRICTED FEEDING ON GLYCOLIPID METABOLISM OF BROWN ADIPOSE TISSUE IN MICE UNDER CONTINUOUS LIGHT EXPOSURE

HU Yu-yu; ZHANG Guan-yu; WU Shuai; LI Xi; LI Jun; YANG Dan-feng

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Acta Nutrimenta Sinica ›› 2026, Vol. 48 ›› Issue (1) : 82-90.

EFFECTS OF TIME- RESTRICTED FEEDING ON GLYCOLIPID METABOLISM OF BROWN ADIPOSE TISSUE IN MICE UNDER CONTINUOUS LIGHT EXPOSURE

HU Yu-yu^1,2, ZHANG Guan-yu², WU Shuai², LI Xi², LI Jun¹, YANG Dan-feng²

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Abstract

Objective To explore the effects of time-restricted feeding (TRF) on glycolipid metabolism in brown adipose tissue (BAT) of mice under continuous light exposure. Methods A total of 132 mice were randomly divided into three groups: a normal light (LD) group, a continuous light (LL) group, and a continuous light plus time-restricted feeding (LL+TRF) group. Each group was further divided into 4 subgroups according to sampling time points (n=11). After 2 weeks of intervention, serum and BAT samples were collected every 6 h starting at 8:00 a.m. on the following day. qPCR was used to detect the mRNA levels of clock genes in BAT within 24 h. Cosine fitting analysis was performed to evaluate the disruption of circadian rhythms in BAT by continuous light and the intervention effect of TRF. Meanwhile, the 24 h expression changes of glycolipid metabolism-related genes in BAT, as well as serum glucose and triglyceride levels, were measured. The protein expression levels of GLUT1 and GLUT4 in BAT were detected by Western blot. Results Compared with the LD group, mice in the LL group showed disrupted feeding rhythms and decreased food intake. The circadian rhythms of multiple core clock genes in BAT were abolished, the expression of glycolipid metabolism-related genes was inhibited, and serum glucose and lipid levels were dysregulated. Compared with the LL group, mice in the LL+TRF group showed downregulated Glut1 expression in BAT and elevated blood glucose levels during the light phase, as well as downregulated Lpl expression in BAT and elevated blood lipid levels during the dark phase. Meanwhile, the expression of key genes involved in de novo lipogenesis in BAT was significantly upregulated in this group. Conclusion Under continuous light exposure, TRF can affect serum glucose and lipid levels by regulating the expression of glycolipid metabolism-related genes in BAT.

Key words

time-restricted feeding / continuous light / glucose and lipid metabolism / brown adipose tissue / mice

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HU Yu-yu, ZHANG Guan-yu, WU Shuai, LI Xi, LI Jun, YANG Dan-feng. EFFECTS OF TIME- RESTRICTED FEEDING ON GLYCOLIPID METABOLISM OF BROWN ADIPOSE TISSUE IN MICE UNDER CONTINUOUS LIGHT EXPOSURE[J]. Acta Nutrimenta Sinica. 2026, 48(1): 82-90

References

[1] Zhang Z, Yan L, Treebak JT, et al. Circadian nutrition: is meal timing an elixir for fatigue?[J]. Sci Bull, 2025, 70: 309–312.
[2] Acosta-Rodríguez V, Rijo-Ferreira F, Izumo M, et al. Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice[J]. Science, 2022, 376: 1192–1202.
[3] Xie Z, Sun Y, Ye Y, et al. Randomized controlled trial for time-restricted eating in healthy volunteers without obesity[J]. Nat Commun, 2022, 13: 1003.
[4] Chen J, Xiang J, Zhou M,#magtechI#et al. Dietary timing enhances exercise by modulating fat-muscle crosstalk via adipocyte AMPKα2 signaling[J]. Cell Metab, 2025, 37: 1364–1380.e6.
[5] Manella G, Sabath E, Aviram R, et al. The liver-clock coordinates rhythmicity of peripheral tissues in response to feeding[J]. Nat Metab, 2021, 3: 829–842.
[6] Xin H, Deng F, Zhou M, et al. A multi-tissue multi-omics analysis reveals distinct kinetics in entrainment of diurnal transcriptomes by inverted feeding[J]. iScience, 2021, 24: 102335.
[7] Zhang Z, Shui G, Li MD.Time to eat reveals the hierarchy of peripheral clocks[J]. Trends Cell Biol, 2021, 31: 869–872.
[8] Yamamuro D, Takahashi M, Nagashima S, et al. Peripheral circadian rhythms in the liver and white adipose tissue of mice are attenuated by constant light and restored by time-restricted feeding[J]. PLoS One, 2020, 15: e0234439.
[9] Acosta-Rodríguez VA, Rijo-Ferreira F, Van Rosmalen L, et al. Misaligned feeding uncouples daily rhythms within brown adipose tissue and between peripheral clocks[J]. Cell Rep, 2024, 43: 114523.
[10] Gong Y, Zhang H, Feng J, et al. Time-restricted feeding improves metabolic syndrome by activating thermogenesis in brown adipose tissue and reducing inflammatory markers[J]. Front Immunol, 2025, 16: 1501850.
[11] Chi S, Zhang T, Pan Y, et al. Time-restricted feeding alleviates metabolic implications of circadian disruption by regulating gut hormone release and brown fat activation[J]. Food Funct, 2023, 14: 10443–10458.
[12] Hepler C, Weidemann BJ, Waldeck NJ, et al. Time-restricted feeding mitigates obesity through adipocyte thermogenesis[J]. Science, 2022, 378: 276–284.
[13] Dewal RS, Yang FT, Baer LA, et al. Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis[J]. iScience, 2024, 27: 108927.
[14] Lapa C, Arias-Loza P, Hayakawa N, et al. Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus[J]. Sci Rep, 2017, 7: 16795.
[15] Cutler HB, Jall-Rogg S, Thillainadesan S, et al. Cold exposure stimulates cross-tissue metabolic rewiring to fuel glucose-dependent thermogenesis in brown adipose tissue[J]. Sci Adv, 2025, 11: eadt7369.
[16] Zheng R, Xin Z, Li M, et al. Outdoor light at night in relation to glucose homoeostasis and diabetes in Chinese adults: a national and cross-sectional study of 98,658 participants from 162 study sites[J]. Diabetologia, 2023, 66: 336–345.
[17] Kim M, Vu TH, Maas MB,,et al. Light at night in older age is associated with obesity. Light at night in older age is associated with obesity, diabetes,hypertension[J]. Sleep, 2023, 46: zsac130.
[18] Obayashi K, Yamagami Y, Kurumatani N, et al. Bedroom lighting environment and incident diabetes mellitus: a longitudinal study of the HEIJO-KYO cohort[J]. Sleep Med, 2020, 65: 1–3.
[19] Baek JH, Zhu Y, Jackson CL, et al. Artificial light at night and type 2 diabetes mellitus[J]. Diabetes Metab J, 2024, 48: 847–863.
[20] Gekakis N, Staknis D, Nguyen HB, et al. Role of the CLOCK protein in the mammalian circadian mechanism[J]. Science, 1998, 280: 1564–1569.
[21] Ye R, Selby CP, Chiou YY, et al. Dual modes of CLOCK: BMAL1 inhibition mediated by cryptochrome and period proteins in the mammalian circadian clock[J]. Genes Dev, 2014, 28: 1989–1998.
[22] Straat ME, Hogenboom R, Boon MR, et al. Circadian control of brown adipose tissue[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2021, 1866: 158961.
[23] van den Berg R, Kooijman S, Noordam R, et al. A diurnal rhythm in brown adipose tissue causes rapid clearance and combustion of plasma lipids at wakening[J]. Cell Rep, 2018, 22: 3521–3533.
[24] 彭景,任保印,张荷,等.生物钟紊乱防治策略的研究进展[J]. 生理学报,2023, 75: 279–290.
[25] van der Veen DR, Shao J, Chapman S, et al. A diurnal rhythm in glucose uptake in brown adipose tissue revealed by in vivo PET-FDG imaging[J]. Obesity (Silver Spring), 2012, 20: 1527–1529.
[26] Mueckler M, Thorens B.The SLC2 (GLUT) family of membrane transporters[J]. Mol Aspects Med, 2013, 34: 121–138.
[27] Nithya U, Theijeswini RC, Karthick Raja R, et al. Glucose transporters and their energy homeostasis function in various organs[J]. Vitam Horm, 2025, 128: 1–47.
[28] Fueger BJ, Czernin J, Hildebrandt I, et al. Impact of animal handling on the results of 18F-FDG PET studies in mice[J]. J Nucl Med, 2006, 47(6): 999–1006.
[29] Din UM, Saari T, Raiko J,,et al. Postprandial oxidative metabolism of human brown fat indicates thermogenesis[J]. Cell Metab. Postprandial oxidative metabolism of human brown fat indicates thermogenesis[J]. Cell Metab, 2018, 28: 207–216.e3.
[30] Rothwell NJ, Stock MJ.A role for brown adipose tissue in diet-induced thermogenesis[J]. Obes Res, 1997, 5: 650–656.
[31] Li Y, Schnabl K, Gabler SM,,et al. Secretin-activated brown fat mediates prandial thermogenesis to induce satiation[J]. Cell. Secretin-activated brown fat mediates prandial thermogenesis to induce satiation[J]. Cell, 2018, 175: 1561–1574.e12.
[32] Pan X, Zhang Y, Wang L, et al. Diurnal regulation of MTP and plasma triglyceride by CLOCK is mediated by SHP[J]. Cell Metab, 2010, 12: 174–186.
[1] Shostak A, Meyer-Kovac J, Oster H.Circadian regulation of lipid mobilization in white adipose tissues[J]. Diabetes, 2013, 62: 2195–2203.
[2] Chua EC, Shui G, Lee IT, et al. Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans[J]. Proc Natl Acad Sci USA, 2013, 110: 14468–14473.
[3] van den Berg R, Noordam R, Kooijman S,#magtechI#et al. Familial longevity is characterized by high circadian rhythmicity of serum cholesterol in healthy elderly individuals[J]. Aging Cell, 2017, 16: 237–243.
[4] Song Z, Xiaoli AM, Yang F.Regulation and metabolic significance of de novo lipogenesis in adipose tissues
[J]. Nutrients, 2018, 10: 1383.
[5] Korobkina ED, Calejman CM, Haley JA, et al. Brown fat ATP-citrate lyase links carbohydrate availability to thermogenesis and guards against metabolic stress[J]. Nat Metab, 2024, 6: 2187–2202.
[6] Meng JJ, Shen JW, Li G,,et al. Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis[J]. Cell. Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis[J]. Cell, 2023, 186: 398–412.e17.
[7] Tsuji T, Tolstikov V, Zhang Y, et al. Light-responsive adipose-hypothalamus axis controls metabolic regulation
[J]. Nat Commun, 2024, 15: 6768.