bims-ciryme 2023-08-27 papers

Issue of 2023‒08‒27
five papers selected by
Gabriela Da Silva Xavier, University of Birmingham

bioRxiv. 2023 Aug 11. pii: 2023.08.11.552890. [Epub ahead of print]

An adult clock component links circadian rhythms to pancreatic β-cell maturation.

Ana P Montalvo, Zoe L Gruskin, Andrew Leduc, Mai Liu, Zihan Gao, June H Ahn, Juerg R Straubhaar, Nikolai Slavov, Juan R Alvarez-Dominguez.

How ubiquitous circadian clocks orchestrate tissue-specific outputs is not well understood. Pancreatic β cell-autonomous clocks attune insulin secretion to daily energy cycles, and desynchrony from genetic or behavioral disruptions raises type 2 diabetes risk. We show that the transcription factor DEC1, a clock component induced in adult β cells, coordinates their glucose responsiveness by synchronizing energy metabolism and secretory gene oscillations. Dec1 -ablated mice develop lifelong hypo-insulinemic diabetes, despite normal islet formation and intact circadian Clock and Bmal1 activators. DEC1, but not CLOCK/BMAL1, binds maturity-linked genes that mediate respiratory metabolism and insulin exocytosis, and Dec1 loss disrupts their transcription synchrony. Accordingly, β-cell Dec1 ablation causes hypo-insulinemia due to immature glucose responsiveness, dampening insulin rhythms. Thus, Dec1 links circadian clockwork to the β-cell maturation process, aligning metabolism to diurnal energy cycles.

DOI: https://doi.org/10.1101/2023.08.11.552890

Chronobiol Int. 2023 Aug 20. 1-10

Does daily energy and macronutrient intake differ between work and non-workdays in shift workers? A mixed methods study.

Manjeet Kaur Saggi, Craig L Phillips, Maria Comas, Camilla M Hoyos, Nathaniel S Marshall, Judith Shu-Chu Shiao, Yue Leon Guo, Ting-Ti Lin, Elizabeth A Cayanan, Christopher J Gordon.

Shift workers are at increased risk of obesity and metabolic diseases, but their eating patterns on work and non-workdays are understudied. We aimed to examine whether energy intake and macronutrient intake of day and night shift nurses were different during work and non-workdays. We used a mixed-methods approach to study food intake of shift working nurses from two hospitals during day and night shifts. Participants completed baseline questionnaires about eating behaviour, sleep, chronotype, mood and shift work disorder. Participants then completed a 4-d food diary which included a non-workday prior to the first shift, the first and last shift (either day or night) and the following non-workday. After completion of the food diaries, we used semi-structured interviews to explore the qualitative aspects of eating behaviours. Seventy-nine shift-working nurses participated in the study. Daily energy intake was not significantly different on work and non-workdays in day or night shift workers (p > 0.05). Whilst macronutrient consumption was also not different between day and night shift workers (p > 0.05), sugar intake was higher in day compared to night shift workers (p = 0.02) on the non-workday prior to the first workday. In qualitative interviews, participants reported their eating to be different on day and night shifts as well as work and non-workdays. Eating behaviour in day and night shift workers was highly influenced by food availability, convenience, peers, and family members. Nurses qualitatively report that night and day shifts result in them eating differently despite no statistically discernible difference in energy intake.

Keywords: Diet; eating behavior; energy intake; night work; shift work

DOI: https://doi.org/10.1080/07420528.2023.2246559

Nat Commun. 2023 Aug 25. 14(1): 5197

Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice.

Jiyeon Lee, Julie M Dimitry, Jong Hee Song, Minsoo Son, Patrick W Sheehan, Melvin W King, G Travis Tabor, Young Ah Goo, Mitchell A Lazar, Leonard Petrucelli, Erik S Musiek.

Alzheimer's disease, the most common age-related neurodegenerative disease, is characterized by tau aggregation and associated with disrupted circadian rhythms and dampened clock gene expression. REV-ERBα is a core circadian clock protein which also serves as a nuclear receptor and transcriptional repressor involved in lipid metabolism and macrophage function. Global REV-ERBα deletion has been shown to promote microglial activation and mitigate amyloid plaque formation. However, the cell-autonomous effects of microglial REV-ERBα in healthy brain and in tauopathy are unexplored. Here, we show that microglial REV-ERBα deletion enhances inflammatory signaling, disrupts lipid metabolism, and causes lipid droplet (LD) accumulation specifically in male microglia. These events impair microglial tau phagocytosis, which can be partially rescued by blockage of LD formation. In vivo, microglial REV-ERBα deletion exacerbates tau aggregation and neuroinflammation in two mouse tauopathy models, specifically in male mice. These data demonstrate the importance of microglial lipid droplets in tau accumulation and reveal REV-ERBα as a therapeutically accessible, sex-dependent regulator of microglial inflammatory signaling, lipid metabolism, and tauopathy.

DOI: https://doi.org/10.1038/s41467-023-40927-1

Cell Metab. 2023 Aug 19. pii: S1550-4131(23)00273-5. [Epub ahead of print]

Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer's disease.

Daniel S Whittaker, Laila Akhmetova, Daniel Carlin, Haylie Romero, David K Welsh, Christopher S Colwell, Paula Desplats.

Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.

Keywords: Alzheimer's mouse models; Alzheimer’s disease; amyloid plaque deposition; circadian rhythms; cognition; hippocampal transcriptome; memory; neuroinflammation; rhythmic transcription; time-restricted feeding

DOI: https://doi.org/10.1016/j.cmet.2023.07.014

Sci Adv. 2023 Aug 25. 9(34): eadh9570

Leptin receptor neurons in the dorsomedial hypothalamus input to the circadian feeding network.

Qijun Tang, Elizabeth Godschall, Charles D Brennan, Qi Zhang, Ruei-Jen Abraham-Fan, Sydney P Williams, Taha Buğra Güngül, Roberta Onoharigho, Aleyna Buyukaksakal, Ricardo Salinas, Isabelle R Sajonia, Joey J Olivieri, O Yipkin Calhan, Christopher D Deppmann, John N Campbell, Brandon Podyma, Ali D Güler.

Salient cues, such as the rising sun or availability of food, entrain biological clocks for behavioral adaptation. The mechanisms underlying entrainment to food availability remain elusive. Using single-nucleus RNA sequencing during scheduled feeding, we identified a dorsomedial hypothalamus leptin receptor-expressing (DMHLepR) neuron population that up-regulates circadian entrainment genes and exhibits calcium activity before an anticipated meal. Exogenous leptin, silencing, or chemogenetic stimulation of DMHLepR neurons disrupts the development of molecular and behavioral food entrainment. Repetitive DMHLepR neuron activation leads to the partitioning of a secondary bout of circadian locomotor activity that is in phase with the stimulation and dependent on an intact suprachiasmatic nucleus (SCN). Last, we found a DMHLepR neuron subpopulation that projects to the SCN with the capacity to influence the phase of the circadian clock. This direct DMHLepR-SCN connection is well situated to integrate the metabolic and circadian systems, facilitating mealtime anticipation.

DOI: https://doi.org/10.1126/sciadv.adh9570