bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2024–10–06
four papers selected by
Gabriela Da Silva Xavier, University of Birmingham



  1. Sci Rep. 2024 09 30. 14(1): 22644
      Physical inactivity as well as breakfast skipping is known as risk factor for various metabolic diseases, such as obesity and type 2 diabetes. We have previously reported that a breakfast skipping model, in which the timing of feeding is delayed, induces abnormal lipid metabolism by altering the circadian rhythm of lipid metabolism-related genes in rats. The purpose of this study was to elucidate the synergistic effect of physical inactivity and breakfast skipping on lipid metabolism. We adopted sciatic neurectomized rats as physically inactive models, because we confirmed that the rats mildly decreased their spontaneous locomotor activity compared to sham-operated rats. And then the physically inactive model rats were fed a mild high-fat diet during zeitgeber time (ZT) 12-0 in the control group and ZT16-0 in the breakfast skipping group for 11 days. Body weight gain and total food intake were similar in both groups. Breakfast skipping induced a significant visceral fat accumulation, which was not observed in our previous breakfast skipping or physically inactive studies. The mRNA levels of clock and lipogenesis-related genes were altered by breakfast skipping in the liver and epididymal adipose tissue, and serum insulin level was altered by breakfast skipping. These results suggest that physical inactivity and breakfast skipping synergistically induces drastic visceral fat accumulation due to the alteration of circadian clock and lipid metabolism in the liver and adipose tissue. Therefore, regular feeding timing plays an important role in the health of a sedentary modern society.
    Keywords:  Breakfast skipping; Circadian rhythm; Lipid metabolism; Physical inactivity; Visceral fat accumulation
    DOI:  https://doi.org/10.1038/s41598-024-68058-7
  2. bioRxiv. 2024 Sep 16. pii: 2024.09.13.612486. [Epub ahead of print]
      Circadian rhythms align biological functions with the 24-hour day-night cycle, but modern artificial light disrupts these patterns, contributing to health issues like obesity and cardiovascular disease. The circadian clock operates through a transcriptional-translational feedback loop involving core components such as BMAL1 and CLOCK. Recent research has shown circadian variations in sphingolipid metabolism, specifically sphingosine-1-phosphate (S1P), which plays crucial signaling roles. This study investigates the sphingolipid enzyme, sphingosine kinase 1 (SphK1), which converts sphingosine to S1P, as a circadian-regulated gene in adipocytes. We find that SphK1 expression and activity follow a circadian rhythm, regulated by BMAL1 and CLOCK binding to its promoter. Adipocyte-specific SphK1 knockout mice exhibit disrupted circadian rhythms, and impaired adipocyte function. Additionally, SphK1 deficiency leads to reduced histone acetylation and altered histone deacetylase (HDAC) localization, affecting gene regulation. These results highlight the critical role of SphK1 in linking lipid metabolism with circadian biology.
    DOI:  https://doi.org/10.1101/2024.09.13.612486
  3. Ann Intern Med. 2024 Oct 01.
       BACKGROUND: Time-restricted eating (TRE), limiting daily dietary intake to a consistent 8 to 10 hours without mandating calorie reduction, may provide cardiometabolic benefits.
    OBJECTIVE: To determine the effects of TRE as a lifestyle intervention combined with current standard-of-care treatments on cardiometabolic health in adults with metabolic syndrome.
    DESIGN: Randomized controlled trial. (ClinicalTrials.gov: NCT04057339).
    SETTING: Clinical research institute.
    PARTICIPANTS: Adults with metabolic syndrome including elevated fasting glucose or hemoglobin A1c (HbA1c; pharmacotherapy allowed).
    INTERVENTION: Participants were randomly assigned to standard-of-care (SOC) nutritional counseling alone (SOC group) or combined with a personalized 8- to 10-hour TRE intervention (≥4-hour reduction in eating window) (TRE group) for 3 months. Timing of dietary intake was tracked in real time using the myCircadianClock smartphone application.
    MEASUREMENTS: Primary outcomes were HbA1c, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycemic assessments from continuous glucose monitors.
    RESULTS: 108 participants from the TIMET study completed the intervention (89% of those randomly assigned; 56 women, mean baseline age, 59 years; body mass index of 31.22 kg/m2; eating window of 14.19 hours). Compared with SOC, TRE improved HbA1c by -0.10% (95% CI, -0.19% to -0.003%). Statistical outcomes were adjusted for age. There were no major adverse events.
    LIMITATION: Short duration, self-reported diet, potential for multiple elements affecting outcomes.
    CONCLUSION: Personalized 8- to 10-hour TRE is an effective practical lifestyle intervention that modestly improves glycemic regulation and may have broader benefits for cardiometabolic health in adults with metabolic syndrome on top of SOC pharmacotherapy and nutritional counseling.
    PRIMARY FUNDING SOURCE: National Institutes of Health.
    DOI:  https://doi.org/10.7326/M24-0859
  4. Sci Rep. 2024 09 28. 14(1): 22476
      Time-restricted eating (TRE) is a nutritional intervention that confines the daily time-window for energy intake. TRE reduces fasting glucose concentrations in non-pregnant individuals, but whether this eating protocol is feasible and effective for glycemic control in pregnancy is unknown. The aim of this randomized controlled trial was to investigate the adherence to and effect of a 5-week TRE intervention (maximum 10 h daily eating window) among pregnant individuals at risk of gestational diabetes mellitus (GDM), compared with a usual-care control group. Participants underwent 2-h oral glucose tolerance tests and estimation of body composition, before and after the intervention. Interstitial glucose levels were continuously measured, and adherence rates and ratings of hunger were recorded daily. Thirty of 32 participants completed the trial. Participants allocated to TRE reduced their daily eating window from 12.3 (SD 1.3) to 9.9 (SD 1.0) h, but TRE did not affect glycemic measures, blood pressure, or body composition, compared with the control group. TRE increased hunger levels in the evening, but not in the morning, and induced only small changes in dietary intake. Adhering to a 5-week TRE intervention was feasible for pregnant individuals with increased risk of GDM but had no effect on cardiometabolic outcomes.
    Keywords:  Continuous glucose monitoring; Diet; Female; Insulin; Obesity; Prevention
    DOI:  https://doi.org/10.1038/s41598-024-72913-y