bims-ciryme 2025-09-14 papers

PLoS One. 2025 ;20(9): e0331218

Exploring the interplay between circadian rhythms and obesity: A Boolean network approach to understanding metabolic dysregulation.

Meitner Cadena, George E Barreto.

This study investigates the interaction between circadian rhythms and lipid metabolism disruptions in the context of obesity. Obesity is known to interfere with daily rhythmicity, a crucial process for maintaining brain homeostasis. To better understand this relationship, we analyzed transcriptional data from mice fed with normal or high-fat diet, focusing on the mechanisms linking genes involved with those regulating circadian rhythms. We performed biological enrichment analysis and Boolean network modeling to identify direct interactions between these genes. The resulting mathematical model provided a comprehensive system of gene interactions, primarily highlighting lipid metabolism. Our findings revealed key insights into the effects of obesity on circadian rhythm genes, particularly the under-expression of core genes such as Bmal1 and Clock. Crucially, we identified a reciprocal interaction between obesity and circadian genes, where disruptions on one exacerbated the dysfunction in the other. This mechanism suggests that the disruption of circadian rhythms plays a pivotal role in worsening the metabolic disturbances associated with obesity, providing new perspectives for targeting circadian pathways in obesity-related metabolic disorders.

DOI: https://doi.org/10.1371/journal.pone.0331218

Nat Commun. 2025 Sep 10. 16(1): 8250

BMAL1-TRIM28 represses transposable elements independently of CLOCK in pluripotent cells.

Amador Gallardo, Efres Belmonte-Reche, María Marti-Marimon, Joan Domingo-Reinés, Guillermo Peris, Lourdes López-Onieva, Iván Fernández-Rengel, Jiajun Xie, Pablo Tristán-Ramos, Nicolas Bellora, Antonio Sánchez-Pozo, Antonio M Estévez, Sara R Heras, Marc A Marti-Renom, David Landeira.

Circadian oscillations of gene transcripts rely on a negative feedback loop executed by the activating BMAL1-CLOCK heterodimer and its negative regulators PER and CRY. Although circadian rhythms and CLOCK protein are mostly absent during embryogenesis, the lack of BMAL1 during prenatal development causes an early aging phenotype during adulthood, suggesting that BMAL1 performs an unknown non-circadian function during organism development that is fundamental for healthy adult life. Here, we show that BMAL1 interacts with TRIM28 and facilitates H3K9me3-mediated repression of transposable elements in naïve pluripotent cells, and that the loss of BMAL1 function induces a widespread transcriptional activation of MERVL elements, 3D genome reorganization and the acquisition of totipotency-associated molecular and cellular features. We propose that during embryogenesis, BMAL1 is redeployed as a transcriptional repressor of transposons in a CLOCK-independent way, and the activity of BMAL1-TRIM28 during prenatal life might protect mammalian organisms from premature aging during adulthood.

DOI: https://doi.org/10.1038/s41467-025-63778-4

BMJ. 2025 Sep 09. 390 e083398

Time restricted eating and exercise training before and during pregnancy for people with increased risk of gestational diabetes: single centre randomised controlled trial (BEFORE THE BEGINNING).

Ma Jafar Sujan, Hanna Ms Skarstad, Guro Rosvold, Stine L Fougner, Turid Follestad, Kjell Å Salvesen, Trine Moholdt.

OBJECTIVE: To determine the effect of a prepregnancy lifestyle intervention on glucose tolerance in people at higher risk of gestational diabetes mellitus.
DESIGN: Single centre randomised controlled trial (BEFORE THE BEGINNING).
SETTING: University hospital in Trondheim, Norway.
PARTICIPANTS: 167 participants with at least one risk factor for gestational diabetes mellitus who contemplated pregnancy.
INTERVENTION: The participants were randomly allocated (1:1) to a lifestyle intervention or a standard care control group. The intervention consisted of exercise training and time restricted eating, started before pregnancy and continued throughout pregnancy. Exercise volume was set using a physical activity metric that translates heart rate into a score (personal activity intelligence, PAI), with the goal of ≥100 weekly PAI points. Time restricted eating involved consuming all energy within ≤10 hours/day for at least five days a week.
MAIN OUTCOME MEASURES: Two hour plasma glucose level in an oral glucose tolerance test at gestational week 28. The primary analysis used an intention-to-treat principle.
RESULTS: 167 participants were enrolled from 2 October 2020 to 12 May 2023: 84 in the intervention group and 83 in the control group, out of whom 111 became pregnant (56 in intervention group and 55 in control group). One participant in the intervention group was excluded from the analysis because of prepregnancy diabetes. Pregnancy data from one participant in the control group were excluded from the analysis because of twin pregnancy. The intervention had no significant effect on two hour plasma glucose level in an oral glucose tolerance test at gestational week 28 (mean difference 0.48 mmol/L, 95% confidence interval -0.05 to 1.01, P=0.08). In the prepregnancy period, 31/83 participants (37%) in the intervention group adhered to prespecified criteria, whereas 24/55 participants (44%) in the intervention group who became pregnant fulfilled these criteria. During the prepregnancy period, the average eating window was 9.9 hours/day (standard deviation 1.2) and the average number of weekly PAI points was 111 (standard deviation 54), but the adherence to both intervention components decreased during pregnancy.
CONCLUSIONS: A combination of time restricted eating and exercise training started before and continued throughout pregnancy had no significant effect on glycaemic control in late pregnancy.
TRIAL REGISTRATION: ClinicalTrials.gov NCT04585581.

DOI: https://doi.org/10.1136/bmj-2024-083398