bims-ciryme 2025-02-23 papers

Front Physiol. 2025 ;16 1515437

Hypothyroidism impairs the circadian rhythmicity of clock genes and proteins involved in gut nutrient absorption in female mice.

Ayla Secio-Silva, Paulo Henrique Evangelista-Silva, Felipe Emrich, Letícia Selvatici-Tolentino, Maíza Ferreira, Ana Bárbara de Paula Silva, Bruno Henrique Gomes, Tatienne Neder Figueira-Costa, André Gustavo Oliveira, Rodrigo Antonio Peliciari-Garcia, Francemilson Goulart-Silva, Paula Bargi-Souza.

Hypothyroidism is a common thyroid dysfunction with a higher prevalence in women. Impairments in the regulation of basal metabolism, small intestine nutrient transporter, dyslipidemia, and disruption in circadian clocks have been associated with the thyroid disorder. This study aimed to evaluate whether hypothyroidism affects the small intestine circadian clock and the daily expression pattern of gut nutrient transporters in female mice. Adult female C57BL/6J mice were subjected to hypothyroidism by the administration of methimazole (0.1%) and sodium perchlorate (1%) in drinking water for 45 days. After, the animals were subdivided and euthanized every 4 h over the 24 h period under deep anesthesia. The proximal small intestine segment was collected and immediately frozen for gene expression analysis of circadian core clock components (Bmal1, Per2, Cry1, and Nr1d1) and nutrient transporters by RT-qPCR. The daily protein content of nutrient transporters involved in the absorption of the products of hydrolysis of lipids, proteins, and carbohydrates was evaluated over 24 h in isolated small intestinal epithelium by Western blotting. The expression of clock genes and protein content of nutrients transporters in the jejunum of control female mice exhibited a well-defined circadian rhythmicity, while no rhythmic oscillation over 24 h was observed for the transporter transcripts. Hypothyroidism abolished the circadian rhythmicity of circadian clock, punctually reduced the transcript content of Slc2a5 (GLUT5) at ZT12 and Slc2a2 (GLUT2) at ZT4, and disrupted the circadian oscillation of L-FABP, CD36, PEPT1, and GLUT2 protein contents in the small intestine of female mice. In conclusion, our findings indicate that thyroid hormones modulate the circadian clock of small intestine and the daily rhythmicity of components related to absorptive processes in female mice. Moreover, our data suggest that the mechanisms triggered by thyroid hormones involve posttranscriptional and/or translational modifications of proteins related to lipid, protein, and carbohydrate absorption. Together, these data contribute to the general comprehension of metabolic alterations often observed in hypothyroidism and have far-reaching implications at clinical levels considering the higher worldwide prevalence of hypothyroidism in women and its association with obesity and metabolic syndrome.

Keywords: circadian clock; female; jejunum; metabolism; thyroid hormones

DOI: https://doi.org/10.3389/fphys.2025.1515437

Front Behav Neurosci. 2025 ;19 1535124

Improved jet lag recovery is associated with a weaker molecular biological clock response around the time of expected activity onset.

Marie-Claire Boutrin, Melissa E S Richardson, Feyikemi Oriola, Samira Bolo.

Introduction: Properly timed environmental light input to the suprachiasmatic nucleus (SCN) in the brain is crucial in maintaining the 24-hour biological rhythm (circadian rhythm). However, light exposure at the wrong time of the day-night cycle is disruptive to circadian-regulated behaviors such as the sleep-wake cycle and memory. While factors such as jet lag, variations in day length, and light at night are known disruptors to the timing of activity onset following rest, the molecular consequence of the intersection of multiple disruptions is less understood.
Methods: Here, we expose mice to a jet lag paradigm under two light-dark (LD) conditions (12:12 LD and 8:16 LD) coupled with additional light exposure at night during the recovery period (known as negative masking), previously demonstrated to improve jet lag-related memory loss in mice.
Results: Our results show that jet lag exposure in both LD cycles (to a greater extent in 8:16 LD) increased the fold-change of circadian gene expression in the SCN relative to the dark onset. The further addition of light during the jet lag recovery period reduced typical changes in circadian gene expression in the SCN to minimal levels under both LD cycles.
Discussion: This study uncovers a novel explanation for the impact of multiple disruptive light exposures on gene expression of the molecular SCN clock in the brain.

Keywords: circadian gene expression; day length; jet lag recovery; master clock; negative masking

DOI: https://doi.org/10.3389/fnbeh.2025.1535124

Proc Natl Acad Sci U S A. 2025 Feb 25. 122(8): e2407907122

Independent effects of the human circadian system and sleep/eating cycles on caloric intake in adolescents vary by weight status.

David H Barker, Mary A Carskadon, Caroline Gredvig-Ardito, Chantelle N Hart, Hollie A Raynor, Frank A J L Scheer.

Late-day eating is linked to increased obesity risk; however, whether the endogenous circadian system independently influences caloric intake and if this control differs among individuals based on weight status is unknown. Here, we investigated in adolescents the independent roles of the endogenous circadian system and of the behavioral sleep/wake cycle (sleep/wake, fasting/eating, rest/activity, dark/dim light, social interaction, posture, etc.) on self-selected caloric intake using a Forced Desynchrony protocol. Fifty-one male and female adolescents across three weight status categories (24 with healthy weight, 13 with overweight, and 14 with obesity) completed the protocol where participants lived on seven 28-h sleep/wake cycles in dim light during wake and complete darkness during sleep. Results suggest that the circadian system and the behavioral cycle each affected caloric intake, with a decrease across the wake episode and an increase from circadian morning to circadian evening in caloric intake. The endogenous circadian rhythm in caloric intake showed a circadian peak-to-trough difference of 196 [CI 95% 164, 226] kcal per meal with peak timing of 296° [288°, 304°; equivalent to ~17:30 in these participants]. In those with overweight/obesity, more calories were consumed later in the waking episode and later in the circadian cycle, and with blunted amplitudes compared to those with healthy weight. Results implicate both the endogenous circadian system and the behavioral cycle in shaping the daily rhythm of food intake. Furthermore, these results help explain the increased drive for caloric intake toward the evening, especially in those at risk for obesity.

Keywords: Forced Desynchrony; adolescent; caloric intake; circadian; weight status

DOI: https://doi.org/10.1073/pnas.2407907122

Diabetologia. 2025 Feb 21.

Associations between the timing of 24 h physical activity and diabetes mellitus: results from a nationally representative sample of the US population.

Qian Xiao, Qiuyu Feng, Martin K Rutter, Gali Albalak, Heming Wang, Raymond Noordam.

AIMS/HYPOTHESIS: Growing evidence suggests that timing may be an important aspect of physical activity that influences cardiometabolic health. However, the current literature is inconclusive regarding the time of day that physical activity offers the greatest metabolic advantages. We investigated associations between hourly physical activity levels and diabetes mellitus and glycaemic biomarkers in a cross-sectional and nationally representative sample of US adults.
METHODS: We studied 7074 adults (mean age 48 years; 52% women) from the National Health and Nutrition Examination Survey (2011-2014). Physical activity was measured by actigraphy. A monitor-independent movement summary (MIMS) unit was used to derive the total activity level (divided into quintiles) for hourly windows that were defined relative to sleep timing and according to clock time. The primary outcome was prevalent diabetes, and secondary outcomes included fasting glucose, fasting insulin, HOMA-IR and 2 h OGTT results.
RESULTS: Physical activity levels in late morning and late afternoon were associated with lower adjusted odds of diabetes. Specifically, in late morning (8:01-9:00 h after the sleep midpoint), the highest quintile of activity was associated with a 35% decrease (OR 0.65; 95% CI 0.44, 0.96) in the odds of diabetes when compared with the lowest quintile, while in late afternoon (11:01-17:00 h after the sleep midpoint), the highest quintiles were associated with 56% and 36% lower odds (OR 0.44; 95% CI 0.29, 0.69 and OR 0.64; 95% CI 0.43, 0.95). Higher night-time activity was associated with higher odds of diabetes. Similar patterns of results were observed with OGTT data and across subgroups of age, gender, race/ethnicity, chronotype and sleep duration.
CONCLUSIONS/INTERPRETATION: Our findings suggest that the timing of physical activity may modulate its metabolic effects.

Keywords: Chronotype; Diabetes; Physical activity; Timing; Type 2 diabetes

DOI: https://doi.org/10.1007/s00125-025-06368-9

Obesity (Silver Spring). 2025 Feb 19.

Time-restricted eating, caloric reduction, and unrestricted eating effects on weight and metabolism: a randomized trial.

OBJECTIVE: Metabolic improvements may precede weight loss. We compared the effects of self-selected 8-h time-restricted eating (TRE), 15% caloric restriction (CR), and unrestricted eating (UE) on weight, body composition, caloric intake, glycemic measures, and metabolic flexibility.
METHODS: In this 12-week randomized-controlled trial, we measured weight (primary outcome), body composition (dual-energy x-ray absorptiometry/magnetic resonance imaging), caloric intake (24-h recall), metabolic flexibility (indirect calorimetry during hyperinsulinemic-euglycemic clamp), and glycemic measures (hemoglobin A1c, hyperinsulinemic-euglycemic clamp, continuous glucose monitoring).
RESULTS: Of the 88 enrolled participants, 81 (92%) completed the trial (mean [SD], age, 43.2 [10.5] years, BMI, 36.2 [5.1] kg/m2; 54.5% female, 84.1% White). Final eating windows were 9.8 h (95% CI: 9.0 to 10.6) for TRE, 12.9 h (95% CI: 11.9 to 13.9) for CR, and 11.8 h (95% CI: 11.0 to 12.7) for UE. Compared with UE (n = 29), weight changes were -1.4 kg (95% CI: -4.5 to 1.7; p = 0.53) with TRE (n = 30) and -2.5 kg (95% CI: -5.8 to 0.8; p = 0.18) with CR (n = 29). TRE showed lower metabolic flexibility than CR (-0.041 [95% CI: -0.080 to -0.002]). Weight, body composition, caloric intake, and glycemic measures were similar among groups. Eating window reduction correlated with decreased caloric intake and visceral fat.
CONCLUSIONS: In a 12-week intervention, TRE did not lead to significant improvements in weight, average body composition, or glycemic or metabolic measures compared with CR or UE.

DOI: https://doi.org/10.1002/oby.24252