| 1. |
- Cedernaes, Jonathan, et al.
(författare)
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Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron
- 2019
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 29:5, s. 1078-1091.e5
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Tidskriftsartikel (refereegranskat)abstract
- The alignment of fasting and feeding with the sleep/ wake cycle is coordinated by hypothalamic neurons, though the underlying molecular programs remain incompletely understood. Here, we demonstrate that the clock transcription pathway maximizes eating during wakefulness and glucose production during sleep through autonomous circadian regulation of NPY/AgRP neurons. Tandem profiling of whole-cell and ribosome-bound mRNAs in morning and evening under dynamic fasting and fed conditions identified temporal control of activity-dependent gene repertoires in AgRP neurons central to synaptogenesis, bioenergetics, and neurotransmitter and peptidergic signaling. Synaptic and circadian pathways were specific to whole-cell RNA analyses, while bioenergetic pathways were selectively enriched in the ribosome-bound transcriptome. Finally, we demonstrate that the AgRP clock mediates the transcriptional response to leptin. Our results reveal that time-of-day restriction in transcriptional control of energy-sensing neurons underlies the alignment of hunger and food acquisition with the sleep/wake state.
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| 2. |
- Kanamori, Mariko, et al.
(författare)
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Community gender norms, mental health, and suicide ideation and attempts among older Japanese adults : a cross-sectional study
- 2023
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Ingår i: International psychogeriatrics. - 1041-6102 .- 1741-203X.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:Gender norms embedded in communities may restrict opportunities and harm the mental health of older adults, yet this phenomenon has received little attention. This study investigates the connection between older adults' perceptions of community gender norms and mental health and suicide-related outcomes.Design:Cross-sectional.Setting:This study analyzed data from the 2019 wave of the Japan Gerontological Evaluation Study.Participants:In total, 25,937 participants aged 65 years or older in 61 municipalities.Measurements:Perceptions of community gender norms were assessed by the respondents' perceptions of the gender-differentiating language used by those around them such as You should/should not do XXX, because you are a man/woman.Results:The prevalence of all mental health outcomes was higher among both men and women who perceived community gender norms as restrictive. These associations remained in fully adjusted multivariable analyses. Prevalence ratios for men were 1.36 [95% confidence interval: 1.13, 1.65] for psychological resistance to obtaining help, 1.85 [1.54, 2.23] for depressive symptoms, 1.99 [1.34, 2.96] for suicidal ideation, and 2.15 [1.21, 3.80] for suicide attempts. The corresponding figures for women were 1.39 [1.17, 1.65], 1.80 [1.55, 2.10], 2.13 [1.65, 2.74], 2.62 [1.78, 3.87]. There was a more pronounced association between perceiving community gender norms as restrictive and depressive symptoms and suicidal behaviors among those with nonconventional gender role attitudes compared to those with conventional attitudes.Conclusions:Considering the effects of community gender norms, in addition to individual gender role attitudes, may be critical in designing effective public health interventions for improving mental health.
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| 3. |
- Levine, Daniel C., et al.
(författare)
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NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding
- 2021
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Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 3:12, s. 1621-1632
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Tidskriftsartikel (refereegranskat)abstract
- In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD+, a cosubstrate of the class III histone deacetylase sirtuin 1 (SIRT1) that associates with clock transcription factors. Although NAD+ also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet (TRF-CR) only during night-time display reduced body temperature and elevated hepatic NADH during daytime. Genetic uncoupling of nutrient state from NADH redox state through transduction of the water-forming NADH oxidase from Lactobacillus brevis (LbNOX) increases daytime body temperature and blood and liver acyl-carnitines. LbNOX expression in TRF-CR mice induces oxidative gene networks controlled by brain and muscle Arnt-like protein 1 (BMAL1) and peroxisome proliferator-activated receptor alpha (PPARα) and suppresses amino acid catabolic pathways. Enzymatic analyses reveal that NADH inhibits SIRT1 in vitro, corresponding with reduced deacetylation of SIRT1 substrates during TRF-CR in vivo. Remarkably, Sirt1 liver nullizygous animals subjected to TRF-CR display persistent hypothermia even when NADH is oxidized by LbNOX. Our findings reveal that the hepatic NADH cycle links nutrient state to whole-body energetics through the rhythmic regulation of SIRT1.
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| 4. |
- Peek, Clara Bien, et al.
(författare)
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Circadian Clock Interaction with HIF1α Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle.
- 2017
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 25:1, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. We show that genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of the hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions. Bmal1(-/-) myotubes displayed reduced anaerobic glycolysis, mitochondrial respiration with glycolytic fuel, and transcription of HIF1α targets Phd3, Vegfa, Mct4, Pk-m, and Ldha, whereas abrogation of the clock repressors CRY1/2 stabilized HIF1α in response to hypoxia. HIF1α bound directly to core clock gene promoters, and, when co-expressed with BMAL1, led to transactivation of PER2-LUC and HRE-LUC reporters. Further, genetic stabilization of HIF1α in Vhl(-/-) cells altered circadian transcription. Finally, induction of clock and HIF1α target genes in response to strenuous exercise varied according to the time of day in wild-type mice. Collectively, our results reveal bidirectional interactions between circadian and HIF pathways that influence metabolic adaptation to hypoxia.
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