更新于：2024-11-01

NR1D1 x NR1D2

更新于：2024-11-01

基本信息

关联

项与 NR1D1 x NR1D2 相关的药物

SR-9009

靶点

NR1D1 x NR1D2

作用机制

NR1D1 刺激剂 [+1]

在研机构-

原研机构

The Salk Institute for Biological Studies

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 NR1D1 x NR1D2 相关的临床结果

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100 项与 NR1D1 x NR1D2 相关的转化医学

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0 项与 NR1D1 x NR1D2 相关的专利（医药）

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项与 NR1D1 x NR1D2 相关的文献（医药）

2024-08-01·Journal of Thermal Biology

Timing of acute cold exposure determines UCP1 and FGF21 expression - Possible interactions between the thermal environment, thermoregulatory responses, and peripheral clocks

Article

作者: Haugen, Fred ; Ryan, Elin ; Dalen, Knut Tomas ; Chau, Phong Kt

Thermoregulation is synchronized across the circadian cycle to uphold thermal homeostasis. To test if time-of-day matters for the response to environmental cold exposure, mice were acclimated to thermoneutrality (27 °C) for 2 months were subjected acutely (8 h) to cold ambient conditions (15 °C), whereas controls were maintained at thermoneutral conditions. The thermal exposure was tested in separate groups (N = 8) at three distinct time-of-day periods: in the LIGHT phase (L); the DARK phase (D); and a mix of the two (D + L). The magnitude of UCP1 protein and mRNA induction in brown adipose tissue (BAT) in response to acute cold exposure was time-of-day sensitive, peaking in LIGHT, whereas lower induction levels were observed in D + L, and DARK. Plasma levels of FGF21 were induced 3-fold by acute cold exposure at LIGHT and D + L, compared to the time-matched thermoneutral controls, whereas cold in DARK did not cause a significant increase of FGF21 plasma levels. Cold exposure affected, in BAT, the temporal mRNA expression patterns of core circadian clock components: Bmal1, Clock, Per1, Per3, Cry1, Cry2 Nr1d1, and Nr1d2, but in the liver, none of the transcripts were modified. Behavioral assessment using the Thermal Gradient Test (TGT) showed that acute cold exposure reduced cold sensitivity in D + L, but not in DARK. RNA-seq analyses of somatosensory neurons in DRG highlighted the role of the core circadian components in these cells, as well as transcriptional changes due to acute cold exposure. This elucidates the sensory system as a gauge and potential regulator of thermoregulatory responses based on circadian physiology. In conclusion, acute cold exposure elicits time-of-day specific effects on thermoregulatory pathways, which may involve underlying changes in thermal perception. These results have implications for efforts aimed at reducing risks associated with the organization of shift work in cold environments.

2023-11-01·Nutrition (Burbank, Los Angeles County, Calif.)

Subcutaneous adipose tissue circadian gene expression: Relationship with insulin sensitivity, obesity, and the effect of weight-reducing dietary intervention.

Article

作者: Stefanowicz, Magdalena ; Karczewska-Kupczewska, Monika ; Strączkowski, Marek ; Nikołajuk, Agnieszka

OBJECTIVEThe circadian rhythms are controlled by the central clock in the hypothalamic suprachiasmatic nuclei and by the peripheral clocks in tissues, including adipose tissue. The adipose tissue circadian clock may be associated with the regulation of insulin action; however, human data are limited. The aim of this study was to analyze the expression of subcutaneous adipose tissue circadian genes as they relate to obesity and insulin sensitivity before and after diet-induced weight loss.METHODSThe study group comprised 38 individuals who were overweight or obese. The individuals completed a 12-wk dietary intervention program. Hyperinsulinemic-euglycemic clamp and subcutaneous adipose tissue biopsy were performed before and after the program. Sixteen normal weight individuals were examined at baseline and served as a control group.RESULTSAt baseline, individuals who were overweight/obese had lower adipose tissue expression of NR1D1, NR1D2, DBP, PER1, and PER2 than normal weight individuals. The expression of ARNTL, CLOCK, and CRY did not differ between the groups. A weight-reducing dietary intervention resulted in an increase in the expression of adipose tissue NR1D2 and DBP, which was positively related to insulin sensitivity both before (in the entire study group and in the subgroup of overweight/obese individuals) and after the dietary intervention.CONCLUSIONSAdipose tissue circadian gene expression is decreased in obesity and this decrease may be partially reversed by dietary intervention. Among circadian genes, NR1D2 and DBP seem to be specifically associated with insulin action.

2023-09-02·Chronobiology International

Association between circadian clock gene expressions and meal timing in young and older adults

Article

作者: Fukazawa, Mayuko ; Tanisawa, Kumpei ; Ito, Tomoko ; Takahashi, Masaki ; Higuchi, Mitsuru ; Shibata, Shigenobu ; Tahara, Yu ; Nakaoka, Takashi ; Kim, Hyeon-Ki

Ageing is associated with a decline in circadian clock systems, which correlates with the development of ageing-associated diseases. Chrononutrition is a field of chronobiology that examines the relationship between the timing of meal/nutrition and circadian clock systems. Although there is growing evidence regarding the role of chrononutrition in the prevention of lifestyle and ageing-related diseases, the optimal timing of meal intake to regulate the circadian clock in humans remains unknown. In this study, we investigated the relationship between clock gene expression and meal timing in young and older adults. In this cross-sectional study, we enrolled 51 healthy young men and 35 healthy older men (age, mean±standard deviation: 24 ± 4 and 70 ± 4 y, respectively). Under daily living conditions, beard follicle cells were collected at 4-h intervals over a 24-h period to evaluate clock gene expression. Participants were asked to record the timing of habitual sleep and wake-up, breakfast, lunch, and dinner. From these data, we calculated "From bedtime to breakfast time," "From wake up to first meal time," and "From dinner to bed time." NR1D1 and PER3 expressions in older adults at 06:00 h were significantly higher than those in young adults (P = 0.001). There were significant differences in the peak time for NR1D2 (P = 0.003) and PER3 (P = 0.049) expression between young and older adults. "From bedtime to breakfast time" was significantly longer in older adults than in young adults. In contrast, "From dinner to bed time" was significantly shorter in older adults than in young adults. Moreover, higher rhythmicity of NR1D1 correlated with longer "From bedtime to breakfast time" (r = -0.470, P = 0.002) and shorter "From wake up to first meal time" in young adults (r = 0.302, P = 0.032). Higher rhythmicity of PER3 correlated with longer "From bedtime to breakfast time" in older adults (r = -0.342, P = 0.045). These results suggest that the peak time of clock gene expression in older adults may be phase-advanced compared to that in young adults. In addition, a longer fasting duration from bedtime to breakfast in both young and older adults and earlier intake of meals after waking up in young adults may correlate with robust clock gene expression rhythms.